Article Category: Clinical

New approach to designing drugs supercharges cancer medication

Shape-shifting drug hits tumors in multiple ways, improves outcomes in mice

Modern anticancer medications that combine tumor-fighting drugs with proteins that specifically target cancer cells are a relatively new class of drug, often given to patients for whom standard chemotherapy has not worked. The drugs are precise, but can attack only one kind of target in the cancer cell at a time. This limits their effectiveness against tumors containing multiple types of targets, which becomes more likely as a cancer progresses or as tumors become resistant to conventional therapies.

Researchers at Washington University School of Medicine in St. Louis have shown in mice that it is possible to increase the potential effectiveness of these drugs, which are known as antibody-drug conjugates. By modifying such drugs already approved by the U.S Food and Drug Administration so that they self-assemble in the body and attack more than one cancer target, the researchers dramatically improved the effectiveness of these medications.

The study was published July 15 in Nature.



“We’ve shown that when two cancer-targeting antibodies bind together inside the body, they accumulate at the tumor more effectively and improve treatment response,” said Patrícia M. Ribeiro Pereira, PhD, an assistant professor of radiology at WashU Medicine Mallinckrodt Institute of Radiology and a research member of Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.

“There is a lot of excitement here because we have shown that it isn’t necessary to create a whole new drug platform for each therapeutic target,” added Ribeiro Pereira. “We can repurpose antibodies that already exist to improve treatments.”

Two drugs in one

In recent years, antibody-drug conjugates have been transforming cancer care, with 15 such drugs approved since 2011 for leukemia and lung, cervical and breast cancer, among others.

The medications combine three components, each with a specialized role. One is the cytotoxic drug that kills a cancer cell when directed to the correct cell. Another is the antibody protein that binds to receptors unique to cancer cells, so that the drug acts specifically within tumors and does not attack healthy tissue. The third is a linking molecule that connects the other two components.

Because each drug can be attached to only one antibody partner, these conjugates are highly specific and attack only cells containing the appropriate receptors. This makes them very effective in relatively homogeneous tumors, but their long-term effectiveness against more complex tumors with a diversity of cell types is limited.

Ribeiro Pereira and her team developed an approach to overcome these limitations using what’s known as click chemistry, a technique that enables adaptable connector molecules to click into a variety of other compounds to form interchangeable molecular structures in a modular way. They created a self-assembling drug apparatus that could tack on a second antibody if needed, thereby doubling the receptor types it could bind to in a tumor.

Both antibodies used in this study are FDA-approved for cancer therapies and target receptors that control tumor growth. One antibody binds to the EGFR receptor; the second, to the HER2 receptor. Another form of the treatment allows two different types of HER2 antibody to bind to different parts of the same receptor, which helps them work together more effectively.

In mice modeling pancreatic, gastric or breast cancer tumors containing cells that expressed EGFR receptors and other cells that expressed HER2 receptors, Ribeiro Pereira’s team first administered an antibody targeting either EGFR or an antibody that binds to a particular portion of the HER2 receptor. The antibodies had all been engineered with one-half of a specialized “click” molecule.

About a day later, the team administered a second type of the HER2 antibody, that binds to a different portion of that receptor, with a drug conjugate and that also carried the complementary click partner. Once in the body, the two antibodies then selectively snapped together. Depending on the approach, the HER2 receptor could be attacked twice as effectively, or both HER2 and EGRF could be targeted at the same time. Both approaches gave the tumor a one-two punch of antibody-drug conjugate — and it made the treatment far more effective than the FDA-approved versions.

Radioactive tags developed by Ribeiro Pereira’s colleagues at WashU Medicine enabled the team to visualize how much drug bound to tumor cells. Ribeiro Pereira and her team found that tumor cells took up much higher amounts of the modified antibody-drug conjugates than is typical for the antibody-drug conjugates that they were derived from, possibly because the click chemistry promotes clustering of antibodies on the cancer cell surface, which enhances internalization by the cell.

Tumors treated with the new form of the drugs resulted in significantly improved survival: as much as 90% of the animals survived 120 days after treatment in the pancreatic model, where animals treated with standard antibody-drug conjugates survived less than 80 days on average. The team also was able to optimize the technique to reduce off-target accumulation of the drug in the liver.

While this study tested the drug in pancreatic, gastric and breast cancer models, Ribeiro Pereira said the modified antibody-drug conjugates have the potential to treat many different tumor types and possibly many other diseases, including some that are currently very difficult to treat with conventional medicine. The linking molecules used in this study only take one to three days to manufacture and allow for greater flexibility when creating precision medicines for individual patients because of the versatile click chemistry approach.

“We’re trying to optimize this tool to help antibodies reach tumors that are normally very difficult to treat, such as brain tumors,” Ribeiro Pereira said. “It’s exciting, because the drug development process doesn’t need to start from the beginning — we can use drugs that are already FDA-approved, which could help bring improved treatments to the clinic more quickly. At the same time, the approach is flexible enough to be adapted to new cancer targets as we learn more about what drives treatment resistance.”

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Simó C, Vanover AC, Albanus RD, Panikar SS, Shmuel S, Benton A, Giraldo-Guzman J, Luna JM, Xu Y, Berry N-K, Keltee N, Liu J, Dehdashti F, Pereira PMR. Modular in vivo antibody-ADC click to reverse drug resistance in tumors. Nature. July 15. DOI: 10.1038/s41586-026-10789-w



Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (R37CA276498 and R21CA291680), internal funds provided by the Mallinckrodt Institute of Radiology, and the American Cancer Society (IRG-21–133–64–03) and the Breast Cancer Alliance. Further support came from the Alvin J. Siteman Cancer Center through The Foundation for Barnes-Jewish Hospital and the National Cancer Institute (P30 CA091842). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Other support came from the W. M. Keck Foundation and the American Cancer Society Award (PF-25-1515996-01-PFCDET), National Institutes of Health (K99AG086583), a Gates Sr. Alzheimer’s Disease Research Fellowship from the Alzheimer’s Disease Data Initiative, the National Cancer Institute of the National Institute of Health under Award Number K22CA282357. The Preclinical Imaging Facility was supported by NIH/NCI Siteman Cancer Center (SCC) Support Grant P30CA091842, NIH instrumentation grants S10OD018515 and S10OD030403, and internal funds provided by the Mallinckrodt Institute of Radiology. TEM and confocal experiments were supported by the Washington University School of Medicine, The Children’s Discovery Institute of Washington University, and St. Louis Children’s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.



About WashU Medicine



WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 3,100 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 78% since 2016. Together with institutional investment, WashU Medicine commits over $1.6 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently among the top five in the country, with more than 2,550 faculty physicians practicing at 200 locations. WashU Medicine physicians exclusively staff Barnes-Jewish and St. Louis Children’s hospitals — the academic hospitals of BJC HealthCare — and Siteman Cancer Center, a partnership between BJC HealthCare and WashU Medicine and the only National Cancer Institute-designated comprehensive cancer center in Missouri and southern Illinois. WashU Medicine physicians also treat patients at BJC’s community hospitals in our region. With a storied history in MD/PhD training, WashU Medicine recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

The Future of Brain Tumor Care is Being Built Now — at Siteman Cancer Center

WashU Medicine experts at Siteman’s Brain Tumor Center are accelerating the science that will create a new standard and new survivorship for brain tumor care

For years, progress against glioblastoma has been measured in small steps with only slight improvements in survival. Now, at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, bold research and remarkable advances against this deadliest form of brain cancer are driving real progress and offering new hope for patients and families.

“We’re at a turning point — a real transition point. We’re potentially on the cusp of breakthroughs over the next five years that we haven’t seen in decades,” said Gregory J. Zipfel, MD, the Ralph G. Dacey Distinguished Professor of Neurological Surgery and chair of the Taylor Family Department of Neurosurgery at WashU Medicine and a founding member of The Brain Tumor Center at Siteman Cancer Center. “But those breakthroughs aren’t going to come from a single discovery — they’re going to come from combining approaches that we are actively investigating and using here.”

Access to clinical trials and second opinion consults are available at The Brain Tumor Center by calling our Siteman care coordinators — oncology-trained nurses who help with scheduling and navigation — at 800-600-3606 or by requesting an appointment here.

Make a referral here.



The Brain Tumor Center at Siteman Cancer Center is recognized internationally for fostering what Zipfel calls “convergence science,” where teams approach understanding and treating brain cancers from all angles — and explore how combination approaches might further advance patient outcomes. That approach is working. In just five years, their work here has moved the needle on effective strategies to treat brain cancers, and they are now poised for major advancements in the treatment of glioblastoma, a particularly aggressive, fast-growing cancer.

WashU Medicine physicians and scientists at Siteman Cancer Center are transforming brain tumor care through the relentless and imaginative pursuit of innovative science and research. Advances in research and clinical trials include developing groundbreaking artificial intelligence (AI) brain-mapping software, initiating groundbreaking radiation and immunotherapy clinical trials, and advancing the use of laser interstitial thermal therapy (LITT) to treat recurrent glioblastoma.

In 2021, Zipfel helped establish The Brain Tumor Center at Siteman Cancer Center, bringing together a team of influential neuro-oncologists, neurosurgeons, radiation oncologists and others focused on providing care attuned to the needs of each patient and aimed at improving lasting outcomes. Working together, the center’s translational researchers, who oversee clinical trials, and basic scientists are focused on creating even better treatment paradigms moving forward.

The Brain Tumor Center at Siteman is led by neurosurgeon Albert H. Kim, MD, PhD, the August A. Busch Jr. Professor of Neurological Surgery and senior vice chair of the Department of Neurosurgery at WashU Medicine. Associate directors are neuro-oncologist Milan G. Chheda, MD, associate professor of medicine and director of neuro-oncology, and radiation oncologist Jiayi Huang, MD, professor of radiation oncology and chief of the CNS/Gamma Knife Service, both also of WashU Medicine.

Other leaders of The Brain Tumor Center are:

  • Research Director Alexander H. Stegh, PhD, who also is a professor of neurosurgery and vice-chair of neurosurgery research at WashU Medicine
  • Caroline H. Ko, PhD, the center’s associate director of research strategy and clinical translation and an associate research professor of neurosurgery at WashU Medicine

Advancing Glioblastoma Treatment Through Translational Science

Even with surgery, chemotherapy and radiation, glioblastoma remains very difficult to treat. Average survival is 15-18 months after diagnosis. Because standard therapies are not curative, the tumor almost always returns.

“The problem isn’t always the main tumor,” Chheda explained. “It’s the microscopic cells that have already spread. Those are what cause recurrence.”

While the primary tumor may be visible and treatable, those microscopic cells often evade therapy. Many are resistant to chemotherapy and radiation. At the same time, the brain itself presents unique barriers. As with the normal brain, brain tumors remain shielded by the blood-brain barrier, a protective network of blood vessels and tissue that prevents entry of many drugs.

“The therapies we currently have are not always reaching the right place, and even when they do, they may not target the right cells,” Chheda said.

Overcoming the challenges of glioblastoma treatment requires more than a single breakthrough. At Siteman, physician-scientists are developing complementary strategies that target the disease from multiple directions — advancing discoveries that are already reshaping how brain tumors are studied and treated here and around the world.

Leaders in Laser Interstitial Thermal Therapy (LITT)

Eric C. Leuthardt, MD, MBA, the Shi H. Huang Professor of Neurological Surgery and vice chair of innovation in the Department of Neurosurgery at WashU Medicine, is a global leader in the research and use of laser interstitial thermal therapy (LITT) to treat glioblastomas and deep-seated brain tumors.

He was one of the first in the country to use LITT for brain cancers when it was cleared by the federal Food and Drug Administration (FDA) in 2010. He has since refined the therapy for minimally invasive tumor ablation and helped to define the national patient criteria for its use.

Leuthardt, Kim and Zipfel are now advancing the use of MRI-guided LITT. A pioneering discovery found that LITT temporarily disrupts the blood-brain barrier, creating a window of opportunity of up to six weeks during which anti-tumor drugs can be used after tumor ablation. They also are investigating how adding checkpoint inhibitors, a type of immunotherapy, into the mix can also improve outcomes.

Research has found that LITT improves the length of survival by up to 40% for certain patients with recurrent glioblastoma. A highly specialized laser ablation surgical suite is now in regular use at Barnes-Jewish Hospital, and the team has performed several hundred LITT procedures, making it one of the busiest centers in the world.

Chheda is rethinking how brain tumors form. Because glioblastoma predominantly occurs in older adults, he is investigating how the aging process itself contributes to brain tumor development.

“You could argue that with time, cells pick up mutations and eventually something goes wrong,” Chheda said. “But it’s also true that the brain itself changes as it ages.”

Instead of viewing glioblastoma as a disease caused by rogue cancer cells, it may also be influenced by changes in the surrounding tissue, called the tumor microenvironment. To Chheda, aging is not just a risk factor. It may also actively influence how tumors emerge, evolve and resist treatment.

“This is a relatively new and exciting area of research, and not many groups are focused on it yet,” he said. “We are exploring how aging alters the brain at a molecular level. By doing so, we may uncover new strategies that can prevent tumor formation, or at the very least, make other treatments more effective.”

Planning Underway for First-in-Human Clinical Trials Using Zika Virus

Ongoing in Chheda’s lab are groundbreaking studies with a modified version of the Zika virus that is engineered to kill glioblastoma. He and colleague Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and professor of molecular microbiology and of pathology and immunology at WashU Medicine, have confirmed that combining the modified Zika virus with standard immunotherapy drugs increased survival rates in mice, from 30% to nearly 90%. The researchers now have created a strain of Zika that is safe for use in humans.

“In mouse models, combining this approach of using Zika-based oncolytic viruses with immunotherapy makes previously ineffective treatments work,” Chheda said. Phase I first-in-human clinical trials are expected to begin before the end of 2026.

Sonobiopsy: Rapidly Advancing New Technology Discovered at Siteman

As multiple researchers explored ways to open the blood-brain barrier to allow for targeted therapies, a team led by Leuthardt and WashU bioengineer Hong Chen, PhD, a professor of biomedical engineering and of neurosurgery and a Siteman research member, invented an ultrasound technology that temporarily opens that barrier. Now called sonobiopsy, the technique uses focused ultrasound and microbubbles to open the blood-brain barrier, which then allows for a non-invasive “liquid biopsy” of the brain tumor, as well as opening the door to add anti-tumor drugs. A first-in-human clinical trial began in 2023 in select patients with high-grade gliomas, including glioblastoma, which originate in the brain or spinal cord.

“What’s remarkable about this is the speed of translation,” Kim said. “It moved from concept to human trials in about three to five years, much faster than normal, which is about a decade. It’s exciting and probably is one of the most significant technological advances coming out of The Brain Tumor Center at Siteman.”

The Most Advanced Radiation Research is Focused on Protecting the Brain

Radiation oncology research is focused on a fundamental challenge: delivering more effective treatment while preserving the healthy brain. Through investigator-initiated and national multicenter clinical trials, WashU Medicine radiation oncologist Jiayi Huang, MD, and colleagues are evaluating innovative approaches designed to improve tumor control, reduce injury to normal tissue and help patients maintain cognitive function throughout treatment. Huang leads pioneering radiation oncology clinical trials that are showing promise in treating glioblastoma.

He is the principal investigator of a multicenter, randomized Phase III clinical trial comparing temporally modulated pulsed radiation therapy (TMPRT) to standard radiotherapy in patients with a type of recurrent glioma, including glioblastomas. TMPRT divides radiation into small pulses with short breaks in between rather than giving radiation to the patient all at once. Early studies found that TMPRT improved survival and preserved cognitive function and memory. The current large-scale study is funded by the National Cancer Institute and conducted through NRG Oncology, one of five national research groups in the NCI’s National Clinical Trials Network. The goal is to enroll almost 400 patients in the Phase III trial over the next four years.

“We think it will control the tumor spread better,” Huang said, “and also cause less injury to normal tissue and less cognitive deficit in patients.”

He is also testing the combination of radiation with an oral agent to enhance immune responses in patients with glioblastoma. Based on his own early-phase investigator-initiated trial, it is hoped that immune-modulating radiation will improve survival. Already, the therapy is moving toward testing in newly diagnosed brain cancer patients later this year.

In a collaboration between neurosurgeons and radiation oncologists, Huang points to the excitement surrounding an industry-led clinical trial that uses radiation seeds implanted into a foam tile that is then placed directly into the brain during surgery to remove a tumor. Called GammaTile, it functions much like the more well-known radiation seeds for prostate cancer.

“The seed itself is not new, and it can move if you insert it into the brain separately,” Huang explained. “Using the seed-implanted foam keeps the seeds in one location to better direct the radiation.”

First Vaccine and Other Innovative Therapies for Glioblastoma

Another major effort involves the development of personalized vaccines tailored to each patient’s brain tumor. A key discovery was that different regions of a tumor can have different mutations. As a result, current clinical trials now sample multiple tumor regions and target shared mutations, improving the effectiveness of treatment options.

Exciting and promising news came just this spring, after an early-stage clinical trial co-led by WashU Medicine researchers at Siteman Cancer Center found that a personalized vaccine to treat glioblastoma is safe and resulted in robust and broad immune responses. The responses appear to increase recurrence-free survival in a subset of patients after surgery.

“We are extremely encouraged by these results,” said lead author Tanner M. Johanns, MD, PhD, assistant professor of medicine at WashU Medicine and a Siteman research member. “This kind of vaccine is a first for glioblastoma, and it is exciting to think how we can leverage this individualized therapeutic DNA cancer vaccine platform to make a positive impact on the lives of patients who are fighting this disease.”

While directly delivering medicines to the brain remains extremely challenging, Stegh and his team have developed a novel drug delivery method that can cross the blood-brain barrier and activate the immune system to attack glioblastoma.

Their technology uses precisely engineered structures assembled from nano-size materials to deliver potent tumor-fighting medicine to the brain through nasal drops. This method is less invasive than similar treatments in development and was shown to be effective in mice. The researchers are now working toward a first-in-human clinical trial.

“This redefines how cancer immunotherapy can be achieved in otherwise difficult-to-access tumors,” Stegh said.

Global Leaders in Advancing Pediatric Brain Tumor Care

In addition to researching effective treatments for adults with brain cancers, The Brain Tumor Center at Siteman has been at the forefront of advancing targeted therapies for children diagnosed with certain types of brain tumors.

WashU Medicine’s Eric M. Thompson, MD, chief of pediatric neurosurgery at Siteman Kids at St. Louis Children’s Hospital, is exploring the effectiveness of a new targeted therapy called moxetumomab pasudotox for children whose brain tumors have not responded well to standard treatment options.

Mohamed Abdelbaki, MD, director of the pediatric brain tumor program at WashU Medicine and Siteman Kids, is investigating another experimental therapy, ONC-212. The tailored therapy attacks cancer cells at the molecular level.

The pediatric brain tumor program at Siteman Kids at St. Louis Children’s Hospital is recognized globally. Abdelbaki founded and leads an international pediatric brain tumor board that comprises experts from around the world who meet regularly to review difficult brain cancer cases. The tumor board has rapidly become the leading consortium of experts committed to collaborative, multidisciplinary discussions that inform recommendations for pediatric brain cancer treatment.

“These studies ensure that innovation in brain tumor care and research reaches patients at every stage of life,” Zipfel said.

One of the Nation’s Most Advanced Brain Tumor Centers

The Brain Tumor Center at Siteman Cancer Center brings together one of the nation’s most comprehensive programs in brain tumor research and care, integrating neurosurgery, neuro-oncology, radiation oncology, advanced imaging, artificial intelligence and translational science to accelerate discovery and improve patient outcomes. That collaborative model is driving innovations ranging from FDA-approved, real-time brain-mapping technology used during surgery to machine learning tools that help predict tumor growth, guide surgical planning and personalize care after treatment.

“Our environment is built for discovery,” said Jiayi Huang, MD. “The Brain Tumor Center and the WashU Jeffrey T. Fort Neuroscience Research Building bring together neurosurgeons, radiation oncologists, physician-scientists and basic researchers in ways that accelerate new ideas into new treatments. That level of collaboration is what distinguishes Siteman and WashU Medicine.”

Albert H. Kim, MD, PhD, director of The Brain Tumor Center, says the program’s scale strengthens both patient care and scientific discovery. Each year, the multidisciplinary team performs more than 700 brain tumor surgeries and cares for approximately 2,000 new patients while training the next generation of surgical and medical neuro-oncology specialists.

“Our goal is not simply to advance today’s standard of care,” Kim said. “It’s to define what the next standard should be.”

WashU Medicine science writer Mark Reynolds contributed to this report.

Siteman Cancer Center Radiation Therapy Recognized for Excellence

Reaccreditation by the American Society for Radiation Oncology underscores Siteman’s enterprise-wide commitment to adult and pediatric patient-centered care

The Department of Radiation Oncology at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, has again been recognized as one of the best radiation oncology centers in the nation.

The recognition comes from its reaccreditation by the American Society for Radiation Oncology (ASTRO), whose 10,000-plus members worldwide — physicians, nurses, physicists, radiation therapists, dosimetrists and other healthcare professionals — specialize in treating patients with radiation therapy.

All seven Siteman Cancer Center locations, including Siteman Kids at St. Louis Children’s Hospital, earned full reaccreditation from ASTRO’s APEx – Accreditation Program for Excellence®, through February 2030. APEx recognizes radiation oncology centers that meet rigorous standards for safety, quality and patient-centered care.

“Achieving APEx reaccreditation across all seven of our sites is a monumental operational achievement,” said Sana Karam, MD, PhD, the Elizabeth H. and James S. McDonnell III Distinguished Professor of Medicine and chair of Radiation Oncology at WashU Medicine and at Siteman Cancer Center. “It reflects the relentless commitment of our entire radiation oncology team — our physicists, dosimetrists, therapists, nurses and physicians. Maintaining this uncompromising standard of safety and quality at such a massive scale is a testament to the true collaborative spirit of WashU and Siteman.”

The Department of Radiation Oncology at Siteman has been APEx-accredited since 2017. Additionally, Siteman’s radiation oncology teams at Barnes-Jewish Hospital and Memorial Hospital Shiloh earned APEx’s new radiopharmaceutical therapy designation. Radiopharmaceuticals, also known as systemic radiation therapy, this year.

Accreditation through APEx is a voluntary and rigorous multi-step process. The enterprise-wide radiation therapy center at Siteman was evaluated using consensus-based standards. Throughout the process, the Department of Radiation Oncology “demonstrated our continued focus on safety and quality and our commitment to patient-centered care, with an emphasis on effective communication, coordinated treatments and strong patient engagement,” Karam said.

Tumor Markers May Help Doctors Decide Which Head and Neck Cancer Patients Need Immunotherapy Before Surgery

WashU Medicine physician-scientists at Siteman Cancer Center identify a promising way to help guide immunotherapy treatment decisions and enhance patient care

Building upon more than a decade of investigator-initiated clinical trials at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, researchers have identified a malignant cell biomarker that may predict which patients will respond to the immunotherapy drug pembrolizumab, known commercially as Keytruda, for the treatment of resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

The research, published March 31 in Cell Reports Medicine, is the latest discovery from one of the nation’s leading head and neck tumor centers, the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center. The findings point to a cell surface protein, major histocompatibility complex class II (MHC-II), as the tumor marker that may help guide treatment decisions. It is typically expressed on immune cells and is important for activating immune responses in the body.

In the study, the researchers found that malignant cells expressing MHC-II and interferon response genes respond better to pembrolizumab administered before surgery, suggesting that a malignant-interferon (IFN)/MHC-II program could be developed into a genomic test to stratify patients into those who should proceed with immunotherapy before surgery and those who should proceed directly to surgery and not be given immunotherapy beforehand.

“Patients with advanced head and neck cancer often undergo immunotherapy prior to and after surgery,” said Sidharth V. Puram, MD, PhD, the Lindburg Professor of Otolaryngology and chair of the Department of Otolaryngology — Head & Neck Surgery at WashU Medicine and co-director of the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center. “The use of immunotherapy drugs, however, means that surgery is delayed by as much as eight to 10 weeks. If we can determine which patients are more likely to benefit from immunotherapy and which ones should go straight to surgery, we can potentially improve overall outcomes for our patients. We think that’s what (IFN)/MHC-II can do: predict how well patients will have a tumor response to immunotherapy.”

Puram is the corresponding author of the study. Co-senior authors are Douglas R. Adkins, MD, director of the Section of Head and Neck and Thyroid Medical Oncology in the Division of Medical Oncology at WashU Medicine and co-director of the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman; Ravindra Uppaluri, MD, PhD, director of Head and Neck Surgical Oncology at Dana-Farber Cancer Institute; and Itay Tirosh, PhD, senior scientist in the Department of Molecular Biology at the Weizmann Institute of Science in Israel.

WashU Medicine researchers already have defined a new standard for the treatment for resectable LA-HNSCC in adults. In the pivotal global KEYNOTE-689 Phase 3 clinical trial, published in the New England Journal of Medicinein June 2025 and co-led by Adkins and Uppaluri, researchers found that the administration of pembrolizumab before and after surgery combined with adjuvant (chemo) radiation therapy resulted in tumor cell death in the surgical specimen and significantly improved the event-free survival (EFS) for these patients.

Perioperative pembrolizumab was approved by the FDA in June 2025 and changed the standard treatment pathway for patients with LA-HNSCC.

“The KEYNOTE-689 trial was built on the favorable results of investigator-initiated trial testing of perioperative pembrolizumab that was developed and conducted at WashU Medicine (with participating sites at the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center),” Adkins said. “In these trials, administration of pembrolizumab before surgery resulted in evidence of tumor cell death in the surgical specimen in up to 50% of patients, a finding linked to better EFS. However, a biomarker was needed that could predict which patients benefited from pembrolizumab before the immunotherapy drug was given. Tumor PD-L1 protein expression does predict potential benefit with pembrolizumab in these patients; however, this test is a very weak predictive biomarker. Predictive biomarkers with stronger links to benefit with pembrolizumab are needed to select patients a priori who may or may not benefit from pembrolizumab before and after surgery.”



To understand the underlying biology and what might drive tumor responses to immunotherapy, researchers used single-cell RNA-sequencing on tissue samples from 16 HNSCC patients, both pre- and post-neoadjuvant pembrolizumab treatment, who were enrolled in the phase 2 trials that represent the predecessors to KEYNOTE-689.



“Single cell approaches allowed us to profile the individual malignant cells and understand the specific genes expressed and how they change with immunotherapy,” Puram said. “Surprisingly, we found a subpopulation of malignant cells that were defined by MHC-II and interferon response genes that predicted immunotherapy response.”



The researchers believe that MHC-II and interferon expression by malignant cells reflects engagement of immune cells with T cells, which are positioned to kill the cancer but have been “turned off” — a state called T-cell exhaustion. Based on spatial techniques, they hypothesize that immunotherapy drugs like pembrolizumab “wake up” these T cells, with MHC-II and interferon identifying which tumors might be poised to then respond to the immunotherapy.



“These results suggest that for the first time, a clinically available strong predictive biomarker may become available to clinicians that can be used to decide whether to include perioperative pembrolizumab before and after surgery and adjuvant therapy for the treatment of patients with LA-HNSCC,” Adkins said. “This will be an important milestone to achieve for our patients.”



“What we’ve demonstrated is the importance of malignant cell states for immunotherapy response,” Puram added. “After more studies with more patients, we envision that a simple test could be developed that tells us if a patient expresses (IFN)/MHC-II and therefore would benefit from immunotherapy. We think this is a significant finding as we continuously try to predict which patients will respond and how to make treatments more effective.”

Historical Clinical and Research Breakthroughs

Siteman Cancer Center has a long history of improving outcomes and driving novel research into head and neck cancers. The WashU Medicine Department of Otolaryngology is among the top 10 recipients of NIH research funding among otolaryngology departments. Within the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center, investigators and physician-scientists across a multidisciplinary team of otolaryngology, medical oncology and radiation oncology specialists oversee one of the largest basic, translational and clinical research portfolios in the country. In addition to paradigm-changing clinical trials such as the KEYNOTE-689 trials, researchers at the center have pioneered advanced reconstructive techniques and new therapies with radiation and chemotherapy, as well as immunotherapies and targeted therapies for head and neck cancers.

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Innovative CAR-T cell therapy receives FDA breakthrough therapy designation

Immunotherapy for aggressive T-cell cancers developed by WashU Medicine researchers moves to faster approval pathway

A cell-based immunotherapy designed to treat rare and aggressive types of blood cancer has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA). Developed by researchers at Washington University School of Medicine in St. Louis, this innovative CAR-T cell therapy is licensed to Wugen, a WashU Medicine startup biotechnology company based in St. Louis’ Cortex Innovation District.

The immunotherapy was developed by WashU Medicine physician-scientists who treat patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.

The therapy — called WU-CART-007 (soficabtagene geleucel) — targets specific blood cancers called T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL). These are aggressive forms of blood cancer that originate in the immune system’s T cells, a type of white blood cell important for the body’s immune response. These cancers often don’t respond at all to standard care or return after several rounds of treatment, leaving patients with few treatment options and poor prognoses. Stem cell transplantation is the only curative treatment for such cancers, but these patients rarely qualify for it because they must first achieve remission following early rounds of chemotherapy, which is rare for these blood cancers.

The FDA’s Breakthrough Therapy designation aims to speed up the development and regulatory review of treatments for serious or life-threatening conditions, especially therapies that may offer substantial improvements over existing options. The Breakthrough Therapy designation for Wugen’s immunotherapy is based on preliminary clinical evidence showing early success in treating these aggressive blood cancers. Early-phase clinical studies have demonstrated that the therapy can selectively target and eliminate cancerous T cells with manageable side effects.

About 1,000 people are diagnosed with T-cell cancers each year in the U.S. If the cancer does not respond to treatment or returns after initial treatment, patients survive an average of six months, and fewer than 7% are still living at the five-year mark.

“This therapy has the potential to enable long-term survival for this patient population by controlling the disease and allowing patients — who would otherwise not be eligible — to proceed to stem cell transplantation, the only potentially curative treatment for these blood cancers,” said WashU Medicine oncologist John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine and director of WashU Medicine’s Center for Gene and Cellular Immunotherapy, who first developed the therapy in his lab at WashU Medicine. “We remain hopeful that the ongoing Phase 2 study will be completed soon, and we’ll have positive results — but we’ll need some time to see how the patients do in both short-term and long-term follow-up.”

DiPersio treats patients at Siteman Cancer Center and founded Wugen alongside other WashU Medicine investigators, including Matthew Cooper, PhD, who then was on the WashU Medicine faculty and now serves as Wugen’s chief scientific officer. The researchers worked with WashU’s Office of Technology Management (OTM) to launch the company in 2018.

The early-phase clinical trial that led to the Breakthrough Therapy designation was conducted in multiple study centers in the U.S., Australia and Europe. The Phase 1 study included 28 adult and adolescent patients with either T-cell lymphoblastic cancer that returned after several lines of therapy or that never responded to treatment. Of 11 patients who could be evaluated after treatment, the overall response rate was 91%, meaning 10 patients either showed no signs of cancer after treatment or their cancer cell burden was reduced significantly. Eight out of 11 patients (72.7%) achieved complete remission. At the study’s data cutoff, six who underwent a transplant remained in remission, with no evidence of disease six to 12 months later, according to the study published in the journal Blood.

“This FDA Breakthrough Therapy designation for soficabtagene geleucel highlights the role of Siteman Cancer Center, a leading NCI-designated Comprehensive Cancer Center, and WashU Medicine in advancing innovative CAR-T cell therapies for aggressive T-cell leukemias and lymphomas,” said Timothy J. Eberlein, MD, director of Siteman Cancer Center and the Spencer T. and Ann W. Olin Distinguished Professor at WashU Medicine. “The dedicated work of our physician-scientists and clinicians is translating the most cutting-edge cellular immunotherapy research into the newest treatment options for patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.”

The phase 2 trial is currently ongoing. At the Siteman site, the clinical trials have been led by principal investigator Armin Ghobadi, MD, a professor of medicine, director of cellular therapies at Siteman, and clinical director of WashU Medicine’s Center for Gene and Cellular Immunotherapy. Siteman Kids at St. Louis Children’s Hospital and WashU Medicine is a key site for the pediatric portion of the clinical trial, co-led by Thomas Pfeiffer, MD, an assistant professor of pediatrics. Ghobadi and Pfeiffer have no financial interest in Wugen.

A major advantage of the treatment is its “off-the-shelf” availability, eliminating the need to manufacture an individualized cell product for each patient. The cell therapy can be prepared in advance from cells donated by healthy individuals and used to treat any patient with a T-cell cancer. In contrast, already-approved CAR-T cell therapies are adapted from the patient’s own immune cells, a process that typically takes three to four weeks. The accelerated treatment timeline of the Wugen immunotherapy reduces logistical and financial barriers associated with most cell-based therapies. This speed can make a meaningful difference because it is not unusual for patients with these aggressive cancers to die while waiting for the therapeutic cells to be prepared.

These particular blood cancers present a unique challenge because the therapeutic cells and the cancer cells are both T cells, so DiPersio and his colleagues came up with further innovations to prevent the therapeutic T cells from mistaking one another for the cancer and causing CAR-T cell fratricide. All other approved CAR-T cell therapies target B cell cancers, which do not have this T cell self-targeting complication.

FDA Breakthrough Therapy Designation Reflects Practice-Changing Trends Only at Siteman

Recognition follows strong early clinical results for a novel off-the-shelf CAR T therapy targeting rare and aggressive T-cell malignancies

A novel off-the-shelf CAR T-cell therapy pioneered at Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine is gaining national recognition after delivering striking clinical results in patients with rare and aggressive blood cancers.

The FDA has granted Breakthrough Therapy Designation to WU-CART-007, an allogeneic anti-CD7 CAR T-cell therapy developed by WashU Medicine researchers. In early global trials, 73% of adults and adolescents with relapsed or refractory (R/R) T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma (T-ALL/LBL) achieved full remission following treatment — an outcome that positions the therapy as a potential gamechanger in T-cell malignancies.

“Relapsed T-cell leukemias and lymphomas represent one of the most challenging areas in hematologic oncology,” said oncologist John DiPersio, MD, PhD, director of the Center for Gene and Cellular Immunotherapy at WashU Medicine and an internationally recognized cell therapy leader at Siteman Cancer Center. “We are leading transformative advances for patients with these rare and aggressive cancers. Developing an off-the-shelf CAR T platform that can induce high remission rates in this population reflects the translational depth and cellular therapy infrastructure we’ve built at Siteman.”

DiPersio and Matthew Cooper, PhD, developed the therapy — manufactured using an off-the-shelf approach from healthy donors — to target CD7+ malignancies. The two founded the biotech company Wugen in 2018 to advance the research. Further clinical trials are underway in the U.S., Europe, Asia and Australia, including at Siteman Cancer Center and Siteman Kids at St. Louis Children’s Hospital.

In reviewing results from earlier clinical trials in children, researchers at Siteman Kids noted that WU-CART-007 (also known as soficabtagene geleucel, or sofi-cel) could be a gamechanger if the therapy continues to move almost all patients from disease-state to remission, thus enabling patients to undergo stem cell transplantation.

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‘An Eco-System of Innovation and Excellence’

The rapid advance of WU-CART-007 is just the latest example of what Timothy J. Eberlein, MD, director of Siteman Cancer Center, says arises out of a robust eco-system of innovation, collaboration and excellence in cancer research at WashU Medicine.

Siteman is known internationally for its basic and translational research efforts and is one of only a few institutions to receive three prestigious Specialized Program of Research Excellence (SPORE) grants from the National Cancer Institute (NCI), for leukemia, endometrial and pancreatic cancer research.

Blood Cancer United, formerly known as the Leukemia & Lymphoma Society, also has awarded scientists at Siteman a Specialized Center of Research (SCOR) grant for lymphoma research. Such grants are specifically designed to accelerate promising translational research into patient care.

“We are committed to continually advancing treatments for cancer and broadening options for patients,” Eberlein said. “Toward that goal, we have initiated several home-grown clinical trials that have changed the course of treatment for many cancers. Our depth and breadth of oncology research is wide, and our expertise is the result of innovation, dedication and multidisciplinary cross-collaboration that occurs throughout our center.”

Other examples of comprehensive, specialized programs at Siteman include the:

Translational Research Highlights

In addition to the latest breakthrough in leukemia and lymphoma research and care, examples of other research efforts that have changed practice guidelines include:

  • New Standard of Care Established for Locally Advanced Head and Neck Cancers — In the first change in standard-of-care therapy in more than 20 years, the FDA approved the use of the immunotherapy drug pembrolizumab (Keytruda) for treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC) in adults. The approval, announced in mid-2025, came after a clinical trial initiated at Siteman in 2013. That trial and later ones, including an international trial, demonstrated greater tumor shrinkage prior to surgery and longer survival rates when immunotherapy was added. “It’s exciting to see our ideas move toward clinical practice with such impressive and potentially life-changing results,” said Douglas Adkins, MD, co-director of the Head and Neck Tumor Center at Siteman, who co-led the clinical trials at Siteman and elsewhere.
  • Addition of Brentuximab Vedotin for Relapsed Diffuse Large B-Cell Lymphoma Results in Statistically Significant Survival Benefit — With approximately 40% of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) having relapsed or refractory disease, researchers at Siteman, led by Nancy Bartlett, MD, found in the ECHELON-Phase Three clinical trial that the use of an antibody-drug conjugate brentuximab vedotin, when combined with either lenalidomide or rituximab, was not only safe but also demonstrated improved survival benefit in patients with R/R DLBCL.
  • Dostarlimab Plus Chemo for Primary Advanced or Recurrent Endometrial Cancer — Matthew Powell, MD, co-led national studies that found adding immune checkpoint inhibitors to standard therapy for endometrial cancer improves outcomes for many patients, with an average increase in overall survival of 31%.
  • T-cell Immunotherapy Effective in Treating Rare Soft Tissue Cancers — Siteman Cancer Center’s Sarcoma program was a major clinical trial site for this study, which found that T-cell immunotherapy, specifically the drug afamitresgene autoleucel, or afami-cel, was effective and generated long-term responses in patients with rare soft tissue cancers.
  • Sotorasib Approved as Targeted Therapy for Patients with Specific Type of Non-Small-Cell Lung Cancer — Following clinical trials at Siteman and globally, the FDA approved sotorasib for patients with non-small-cell lung cancer whose tumors express a G12C mutation in the KRAS gene and who have already undergone previous treatment. Ramaswamy Govindan, MD, who led the study, noted that the drug targeted the most common mutation, reduced tumor sizes, and improved overall survival rates.
  • Medicare Approves Whole-Genome Test for Blood Cancers — A test for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) developed at Siteman was the first whole-genome sequencing test for cancer to be approved for reimbursement by the Centers for Medicare & Medicaid Services. Called ChromoSeq, the test is now routinely used by oncologists to guide treatment decisions for patients with blood cancers.

“At Siteman, we have built one of the world’s leading cellular immunotherapy programs focused on developing next-generation treatments for rare and refractory cancers,” Eberlein said. “Many of our most impactful cell therapy trials are investigator-initiated and originated here, reflecting a translational infrastructure designed to bring innovative therapies to patients with the most aggressive and rarest cancers.”

Gary C. Werths building at Siteman earns LEED Gold

Project team identified more environmentally friendly solutions throughout the building process

The Gary C. Werths Building at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, has earned Leadership in Energy and Environmental Design (LEED) Gold certification from the U.S. Green Building Council. Buildings that achieve this recognition must meet stringent criteria in categories such as energy efficiency, water conservation and material recycling — all indicators of lower environmental impact. The nine-story Werths Building opened in September 2024 on the Washington University Medical Campus.

While numerous factors such as monitoring energy use and improving air quality contributed to the accomplishment, the WashU Medicine Operations and Facilities Management team’s embodied carbon effort set it apart. The Embodied Carbon Program was developed by WashU Medicine and the Werths Building’s project management team. It involves maintaining a comprehensive inventory of materials used during a building’s design, procurement and construction, and identifying more environmentally friendly alternatives throughout the process. Carbon-conscious decision-making informed everything from choosing more eco-friendly carpet and concrete to preventing unnecessary transportation and construction waste.

In total, WashU Medicine’s energy reduction efforts have avoided 4.2 million kg Co2e in emissions, equivalent to 208 garbage trucks of waste recycled instead of sent to a landfill. WashU Medicine has since incorporated the Embodied Carbon Program into its design standards for future projects and has provided training on it for the WashU Office of Sustainability.

The Werths Building provides a healing environment for patients, with the design focused on their comfort and convenience and reducing the need to return for multiple appointments. Within its walls, WashU Medicine physicians also offer access to more than 600 clinical trials designed to assess the effectiveness of innovative treatments and applications for people with various cancer types.

The LEED point system is widely recognized as the industry standard for green buildings in the United States and more than 160 countries around the world. The more points a building earns, the higher its LEED rating will be. There are four levels of LEED certification: Certified (40-49 points), Silver (50-59 points), Gold (60-79 points) and Platinum (80+ points). The Werths Building was awarded all 65 points that were submitted.

Connecting cancer patients to tobacco treatment is aim of $7.5 million, WashU-led trial

Cancer patients who quit smoking live significantly longer than those who don’t

The science is clear: Cancer patients who quit smoking fare much better than those who don’t. Quitters respond better to treatment and are less likely to see their disease come back or develop a new cancer, and they have a lower risk of other serious conditions such as heart disease. Quitting is hard, but people who participate in evidence-based tobacco-treatment programs are three times more likely to succeed in kicking the habit.

Still, despite the proven benefits of quitting, most cancer patients and survivors who smoke never receive treatment for their tobacco use.

A large-scale, multicenter trial led by researchers at Washington University in St. Louis aims to reduce the burden of cancer by getting more survivors the support they need to quit smoking. The trial — a four-year study to be conducted at 72 cancer centers across eight states, including Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine — will test different clinic-based approaches to connecting cancer survivors to tobacco treatment. The goal is to develop evidence-based recommendations on how to choose, implement and sustain an effective tobacco-treatment strategy at a cancer clinic.

“Even though smoking cessation is part of the standard of care, six out of seven patients with cancer who smoke are not getting any tobacco treatment, so they continue to smoke, and eventually they die early,” said Li-Shiun Chen, MD, MPH, ScD, a professor of psychiatry at WashU Medicine and one of three principal investigators on the trial. “That’s a big missed opportunity. We already know an important way to reduce cancer deaths, and we’re not implementing it.”

Chen and the two other principal investigators — Ross Brownson, PhD, and Alex Ramsey, PhD — are research members at Siteman.

A previous effort to integrate tobacco cessation into cancer care nationwide revealed sobering results. In 2017, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative, an ambitious plan to roll out tobacco-treatment programs at the then-52 NCI-designated Comprehensive Cancer Centers nationwide. A five-year analysis revealed that the centers had succeeded in connecting only 15% of their cancer patients with such care, with huge variation in connection rates across centers.

“Scaling up is not a simple thing,” said Brownson, who is also the Steven H. and Susan U. Lipstein Professor at the WashU School of Public Health. “Many of these centers used similar strategies, but the results were varied. We need to understand why a strategy that was effective for one center didn’t work at another one, and what alternative strategy would be more effective.”

That need drove Chen, Brownson and Ramsey, who is also an associate professor of psychiatry at WashU Medicine, to propose the Implementation Science to Scale and Sustain Tobacco Treatment Leveraging a Point of Care Paradigm and Health Information Technology (IMPACT) trial. The three researchers co-lead the trial in collaboration with experts and colleagues at the University of Pennsylvania, Vanderbilt University Medical Center and the St. Louis VA Medical Center. The trial, which will be implemented at cancer clinics affiliated with the four hub sites, aims to determine how to match strategy to clinic, taking into consideration such factors as the size of a clinic, the barriers to receiving care faced by its patients, and the institutional support and resources available. The WashU team is implementing the trial at clinics affiliated with Siteman, where Chen serves as director of the Tobacco Treatment Program.

The trial is supported by a $6.9 million grant from the NCI, with an additional $600,000 provided by Siteman. It is one of four projects in the NCI’s Scaling-up and Maintaining Evidence-based Interventions to Maximize Impact on Cancer (SUMMIT) initiative, a major investment in improving cancer prevention and control by studying how to implement proven interventions in real-world settings.

As part of the trial, each clinic will be randomized to one of four strategies: usual care, referral to a specialist, point of care, or combined referral and point of care. The referral strategy is the most common way of getting patients into tobacco care: The oncologist asks about smoking during a regular visit and refers those who answer yes to a tobacco-treatment specialist. The patient then makes an appointment to meet the specialist at a separate visit. The strategy can work well when a cancer center is able to fund enough tobacco specialists, and patients have the time, resources and willingness to add more appointments to their calendars.

The point-of-care model was developed by Chen and colleagues at Siteman during a time when no tobacco-treatment specialists were on staff. In this model, all hands are on deck: Medical assistants, staff nurses, and nurse practitioners conduct the tobacco-use assessment, provide brief advice to quit smoking and queue cessation medication orders for the clinician to prescribe. They also refer patients to free phone, text or app-based cessation services such as Quitline, a phone-based service available nationwide at 1-800-QUIT-NOW; text messaging cessation services, reachable by texting QUITNOW to 333888; or an app supported by Smokefree.gov. In a recent study, Chen and colleagues showed that a point-of-care approach can be very effective at helping cancer patients quit smoking and improving outcomes.

The record of the Cancer Center Cessation Initiative suggests that many of the clinics may not initially succeed with the strategy they are assigned. Those that are unable to connect at least 15% of eligible patients to tobacco treatment after 18 months will be offered the options of continuing the current strategy, if more time is thought to be helpful; trying a different strategy; or modifying their strategy to include personalized tobacco-treatment plans based on each patient’s unique genetic, clinical and environmental factors.

In those clinics that do succeed, the focus will shift to sustainability. New clinical practices, even successful ones, are at risk of being abandoned when funding ends or priorities change. To minimize this risk, clinics will be provided either general sustainability support, or clinic-specific support based on data from the Clinical Sustainability Assessment Tool. The validated tool — developed at WashU Public Health’s Center for Public Health Systems Science — provides a systematic way to assess the factors that promote sustainability of clinical practices.

“Even when we know what treatments or prevention tools work, we don’t know enough about how we can implement them quickly, scale them up more widely or sustain them long enough,” Ramsey said. “The ultimate goal is to make sure that every single cancer patient who smokes is engaged with treatment, but the route to get there is going to be different for each clinic. We need to figure out which strategies will work best in which context, so we can use the evidence-based tools we already have to improve people’s health.”

Learn about smoking cessation tools available to our patients and community members.

New center to develop AI-based imaging tools to improve diagnosis, care

WashU Medicine Mallinckrodt Institute of Radiology leads effort on image-based precision medicine

Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis is establishing a new center dedicated to developing AI-based imaging tools to improve the diagnosis and precision treatment of cancers, cardiovascular disease, neurological diseases and numerous other conditions. The new Center for Computational and AI-enabled Imaging Sciences brings together collaborators from across WashU Medicine — including Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine — and others from WashU’s McKelvey School of Engineering.

AI already has shown promise for its ability to analyze vast collections of medical images to generate clinically relevant insights, identifying patterns and anomalies that physicians might otherwise not detect on their own.

“Mallinckrodt Institute of Radiology has long been a national leader in developing innovative imaging technologies, from the invention of positron emission tomography to today’s AI applications in diagnostics and image analysis, and this new center represents an ambitious expansion of our capability,” said Pamela K. Woodard, MD, the Elizabeth E. Mallinckrodt Professor and head of MIR at WashU Medicine. “Integrating AI into imaging will enhance how we diagnose disease, predict its progression and tailor treatments to the unique needs of each patient.”

The new center will help advance AI-driven imaging technologies, such as two recently developed at WashU Medicine — in collaboration with MIR — that are being commercialized. One tool can analyze mammograms to predict an individual patient’s risk of breast cancer over the next five years. Another rapidly maps the brain to help neurosurgeons plan delicate surgeries and avoid sensitive areas that control speech, movement and cognitive function. The center will be a hub for expertise in image analysis that uses sophisticated computing tools to find patterns in datasets of millions of medical images and de-identified patient records, providing insight on both the progression and the potential treatment of disease. The center will also support training on these tools for clinicians and researchers.

The new center will join a growing WashU ecosystem of collaborative AI initiatives that are helping to shape the future of medicine. These include the Center for Health AI (CHAI), which was established as part of the joint agreement to build deeper collaboration between BJC Health System and WashU Medicine and is focused on making health care more personalized and effective for patients and more efficient for providers; and the AI for Health Institute at WashU McKelvey Engineering, which is working on other AI-powered medical innovations.

The Center for Computational and AI-enabled Imaging Sciences will primarily focus on developing AI-based medical imaging applications that integrate information from different imaging types — ranging from digital microscope images of cells to MRI scans to X-rays — to identify clinically informative connections between them. This may include identifying previously unknown early indicators of disease onset that could allow for more effective clinical interventions.

The center will bring together AI imaging experts and researchers from across the Medical Campus, including Siteman Cancer Center, and from the school’s Departments of Medicine, of Neurology, of Psychiatry and of Radiation Oncology.

A Clear Image of the Future of Medicine

The new center will house information from the imaging databases of all the participating departments, collectively representing a range of imaging modalities across many different types of disease. The AI-powered tools developed from those large datasets will enable increasingly precise diagnosis for individual patients, Woodard said.

AI algorithms applied to medical imaging have already been used to detect and classify new subtypes of some disorders in ways that can guide clinical treatment decisions. The breadth of information that will be available at the new center will accelerate this work in a broader range of conditions.

The new center will be led by Mark Anastasio, PhD, a leading expert in computational imaging science and AI for imaging applications. He joins WashU as the Mallinckrodt Endowed Professor of Imaging Sciences for MIR, where he will also be the Vice Chair for Imaging Sciences and AI Research. He will also be Professor of Electrical & Systems Engineering in McKelvey Engineering. Anastasio comes to WashU from the University of Illinois Urbana-Champaign, where he has served as head of the Department of Bioengineering for the past six years.

“Institutions with leading academic medical centers that unite medical data, clinical expertise and advanced AI research will lead the next revolution in healthcare,” said Anastasio. “WashU is exactly such an institution and an ideal home for this center that will enable us to build a community to drive innovation that advances patient care in ways few other institutions can achieve.”

As part of that community building, Anastasio will join the leadership team of the Oncologic Imaging Program at Siteman Cancer Center. He will also be the associate Chief Research Information Officer for Biomedical Imaging at the Institute for Informatics, Data Science & Biostatistics (I2DB), where he will work with institute director Philip R.O. Payne, PhD, the Janet and Bernard Becker Professor of Medicine. Payne is also the chief health AI officer for CHAI and the Vice Chancellor for Biomedical Informatics and Data Science at WashU Medicine.

“AI-enabled imaging has the potential to be as transformative for medicine as earlier waves of innovation — from the adoption of electronic health records to the rise of precision medicine and the advent of real-world evidence generation,” said Payne. “That transformation is being realized here at WashU Medicine because of the dynamic and collaborative environment that exists at our institution, exemplified by leading-edge, transdisciplinary initiatives like this one.”

Aaron Bobick, PhD, dean of WashU McKelvey Engineering and the James M. McKelvey Professor, said dedicated centers such as this will be crucial to maximizing the medical and engineering expertise needed to build out the potential for AI in medical applications.

“Medical imaging offers some of the most exciting challenges in imaging science and artificial intelligence, both of which are core domains for McKelvey Engineering,” said Bobick. “I am certain that the innovations that this center will facilitate by combining the skills of WashU Engineering faculty with the broad range of medical expertise at WashU Medicine will lead to advances that both drive the science forward and benefit patients.”

1,000th patient treated at Siteman with AI-enabled radiation therapy system

Combining artificial intelligence (AI) with advanced imaging, the technology supports more precise, personalized daily treatments by WashU Medicine physicians

Siteman Cancer Center at Barnes-Jewish Hospital and WashU Medicine has treated its 1,000th patient using state-of-the art radiation therapy technology that allows physicians to update a patient’s treatment plan on each day of treatment.

Called adaptive technology, the system incorporates slight changes in tumor shape, size and location, as well as the movement of surrounding healthy organs and tissue, to adjust a patient’s daily radiation therapy treatment plan for the best possible outcome.

The system is used to treat a range of tumors, including head and neck, central nervous system, thoracic, abdominal and pelvic cancers.

“We are pleased to offer this advanced technology to our patients — from the first person we treated with this system in 2020, to the 1,000th person in August 2025,” said WashU Medicine radiation oncologist Hyun Kim, MD, associate professor of radiation oncology and chief of Adaptive Radiation Therapy at WashU Medicine and Siteman.

“The milestone of 1,000 patients treated on this platform is literally the result of thousands of hours dedicated by our faculty and staff to personalize treatment every day for every patient,” he said.

Also known as online adaptive radiation therapy, it requires a team of expert physicians, physicists and radiation therapists to develop and review a treatment plan after the patient’s arrival — all within minutes after the patient is positioned to receive treatment.

In addition to the AI component and machine learning, the platform is equipped with cone-beam computed tomography (CT). Cone-beam CT quickly provides high-quality images and leads to better visualization of the tumors and surrounding healthy organs and tissue, allowing the physician to develop even more accurate, personalized treatment plans than with some older radiotherapy platforms.

In clinical trials incorporating the new technology, patients experienced decreased times to treatment and, in some cases, improved cancer control with less damage to surrounding healthy organs and tissue.

For some gynecologic cancers, treatment can involve imaging the ovaries of pre-menopausal patients. As a result, some patients have experienced premature ovarian failure and early menopause when treated with older radiotherapy technologies. WashU Medicine physician-scientists are conducting an ongoing clinical trial using the new technology with the hope that they can spare these organs.

Known as Ethos, the platform is manufactured by Varian Medical Systems, which also makes the cone-beam CT imaging component, called HyperSight.