Article Category: In the Media

Drug bypasses suppressive immune cells to unleash immunotherapy

By recruiting the immune system to combat tumor cells, immunotherapy has improved survival rates, offering hope to millions of cancer patients. However, only about one in five people responds favorably to these treatments.

With a goal of understanding and addressing immunotherapy’s limitations, researchers at Washington University School of Medicine in St. Louis have found that the immune system can be its own worst enemy in the fight against cancer. In a new study in mice, a subset of immune cells – type 1 regulatory T cells, or Tr1 cells – did its normal job of preventing the immune system from overreacting but did so while inadvertently restraining immunotherapy’s cancer-fighting power.

“Tr1 cells were found to be a heretofore unrecognized obstacle to immunotherapy’s effectiveness against cancer,” said senior author Robert D. Schreiber, PhD, the Andrew M. and Jane M. Bursky Distinguished Professor in the Department of Pathology & Immunology, and director of the Bursky Center for Human Immunology & Immunotherapy at Washington University School of Medicine. “By removing or circumventing that barrier in mice, we successfully reenergized the immune system’s cancer-fighting cells and uncovered an opportunity to expand the benefits of immunotherapy for more cancer patients.”

The study is available in Nature. Schreiber is a research member of Siteman Cancer Center, which is based at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis.

Cancer vaccines represent a new approach to personalize cancer immunotherapy. Aimed at the mutant proteins specific to a patient’s tumor, such vaccines induce killer T cells to attack tumor cells while leaving healthy cells unharmed. Schreiber’s group previously showed that more effective vaccines also activate helper T cells, another immune cell type, that recruit and expand additional killer T cells to destroy the tumors. But when they tried to add increased amounts of the helper T cell target to supercharge the vaccine they found they generated a different type of T cell that inhibited rather than promoted tumor rejection.

“We tested the hypothesis that by increasing helper T cell activation we would induce enhanced elimination of the sarcoma tumors in mice,” said first author Hussein Sultan, PhD, an instructor in pathology & immunology. So he injected groups of tumor bearing mice with vaccines that activated killer T cells equally while triggering a different degree of helper T cell activation.

Much to the researchers’ surprise in this latest study, the vaccine meant to hyperactivate helper T cells produced the opposite effect and inhibited tumor rejection.

“We thought that more helper T cell activation would optimize elimination of the sarcoma tumors in mice,” Sultan said. “Instead, we found that vaccines containing high doses of helper T cell targets induced inhibitory Tr1 cells that completely blocked tumor elimination. We know that Tr1 cells normally control an overactive immune system, but this is the first time they have been shown to dampen its fight against cancer.”

Tr1 cells normally put the brakes on the immune system to prevent it from attacking the body’s healthy cells. But their role in cancer has not been seriously explored. Looking through previously published data, the researchers found that tumors from patients who had responded poorly to immunotherapy had more Tr1 cells compared with tumors of patients who had responded well. The number of Tr1 cells also increased in mice as tumors grew bigger, rendering the mice insensitive to immunotherapy.

To bypass the inhibiting cells, the researchers treated the vaccinated mice with a drug that enhances killer T cells’ fighting power. The drug, developed by biotechnology startup Asher Biotherapeutics, carries modifications in the immune-boosting protein called interleukin 2 (IL-2) that specifically revs up killer T cells and reduces the toxicity of unmodified IL-2 treatments. The additional boost from the drug overcame Tr1 cells’ inhibition and rendered the immunotherapy more effective.

“We are committed to personalizing immunotherapy and broadening its effectiveness,” said Schreiber. “Decades of researching basic tumor immunology have expanded our understanding of how to trigger the immune system to achieve the most robust antitumor response. This new study adds to our understanding of how to improve immunotherapy to benefit more people.”

As co-founder of Asher Biotherapeutics – which provided the mouse version of the modified IL-2 drugs – Schreiber is indirectly involved in the company’s clinical trials testing the human version of the drug as a monotherapy in cancer patients. If successful, the drug has the potential to be tested in combination with cancer treatment vaccines.

Some sarcoma patients improve with T cell immunotherapy

Strategy effective against some rare, aggressive sarcomas with no other treatment options

A clinical trial led by researchers at Washington University School of Medicine in St. Louis has shown that a T cell immunotherapy — in which the patients’ own T cells are genetically modified to attack and kill cancer cells — is effective in treating some patients with rare cancers of the body’s soft tissues.

The study, which focused on the rare cancers synovial sarcoma and myxoid round cell liposarcoma (MRCLS), is inThe Lancet.


“When these rare sarcomas have spread, patients have few treatment options, and five-year survival rates are very low,” said senior author Brian A. Van Tine, MD, PhD, a Washington University professor of medicine who treats patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine. “There is a great need for more effective therapies, but standard immunotherapies don’t work well for sarcomas. With this T cell immunotherapy, there is a subset of patients who have experienced an excellent long-term response. But for some patients, the treatment works for a little while and the cancer returns; and for others, it doesn’t work at all. We are hopeful we can build on the success of this clinical trial and make this type of therapy effective for more patients.”


The investigational immunotherapy that was used in the trial, called afamitresgene autoleucel (afami-cel), involves collecting a patient’s T cells and engineering them in the lab with a viral vector, a virus designed to deliver genetic material into cells. The viral vector adds a specific protein onto the surface of the T cells. When the modified T cells are returned to the patient, the new surface protein — a T cell receptor — directs the T cells to home in on the cancer cells for elimination. Most of these types of sarcomas have a protein on their surface called MAGE-A4, which the newly engineered T cells can then seek and destroy.


The immunotherapy was developed by the biopharmaceutical company Adaptimmune, which funded the international clinical trial. Siteman, which is a major referral center for sarcoma patients nationally, was one of the trial’s major sites.


The clinical trial involved 52 patients treated at 23 medical centers in North America and Europe. The trial included 44 patients with synovial sarcoma and eight with MRCLS. To participate in the trial, patients’ immune systems had to meet certain criteria in how they present antigens to T cells, to teach the T cells to identify the cancer.


About 36% of the patients (19 of 52) responded to the therapy with tumors shrinking or, in some cases, disappearing entirely. The treatment was more effective for patients with synovial sarcoma than with MRCLS. On average, the duration of the tumor response was just over 11 months for patients with synovial sarcoma and just over four months for patients with MRCLS; most patients’ cancers returned after a period of remission. To date, a small number of patients whose tumors disappeared following initial therapy remain cancer-free.


Among all of the patients, average survival was just over 15 months. The probability of survival at one year was 60%. Among patients with synovial sarcoma whose tumors showed a complete response to initial therapy — meaning the tumors disappeared entirely following the single treatment — the probability of survival was 90% at one year and 70% at two years.


The most common side effects of the treatment involved low red and white blood cell counts due to the chemotherapy needed to prepare the body to receive the engineered T cells. Many of the patients required treatment to control cytokine release syndrome, a common inflammatory response to T cell therapies. All 28 deaths that occurred during the follow-up period were found to be due to the cancer eventually progressing and not the investigational treatment.


“We have some patients we’re still watching who continue to have a deep, durable response to this single treatment,” Van Tine said. “In some cases, the engineered T cells can get into the bone marrow and establish a niche, and these patients haven’t needed further treatment. As long as the T cells continue to divide and the tumor continues to carry the target protein, it’s an effective therapy in these patients. We’re trying to understand what is different about the individuals who do so well, so we can extend this type of effect to more patients in the future.”


D’Angelo SP, Araujo DM, Razak ARA, Agulnik M, Attia S, Blay J, Garcia IC, Charlson JA, Choy E, Demetri GD, Druta M, Forcade E, Ganjoo KN, Glod J, Keedy VL, Le Cesne A, Liebner DA, Moreno V, Pollack SM, Schuetze S, Schwartz GK, Strauss SJ, Tap WD, Thistlethwaite F, Morales CMV, Wagner MJ, Wilky BA, McAlpine C, Hudson L, Navenot J, Wang T, Bai J, Rafail S, Wang R, Sun A, Fernandes L, Van Winkle E, Elefant E, Lunt C, Norry E, Williams D, Biswas S, Van Tine BA. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. The Lancet. March 27, 2024.


This work was supported by Adaptimmune. Van Tine reports no financial interest in Adaptimmune.


About Washington University School of Medicine


WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, 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.


Writer: Julia Evangelou Strait, Senior Medical Science Writer | 314-286-0141 | [email protected]


Media Contact: James Goodwin, Associate Director of Strategic Communication, Siteman Cancer Center | 314-680-8251 | [email protected]

AI may predict spread of lung cancer to brain

Method may inform personalized cancer treatments

Physicians treating patients with early-stage lung cancer face a conundrum: choosing potentially helpful yet toxic therapies such as chemotherapy, radiation or immunotherapy to knock out the cancer and lessen the risk of it spreading to the brain, or waiting to see if lung surgery alone proves sufficient. When up to 70% of such patients do not experience brain metastasis — the spread of cancer to the brain — the question arises: Who should receive additional aggressive treatments, and who can safely wait?

A new study led by Washington University School of Medicine in St. Louis could help physicians strike the right balance between proactive intervention and cautious monitoring for patients with early-stage lung cancer. The study, published March 4 in The Journal of Pathology, uses an artificial intelligence (AI) method to study patients’ lung biopsy images and predict whether the cancer will spread to the brain.

“There are no predictive tools available to help physicians when treating patients with lung cancer,” said Richard J. Cote, MD, the Edward Mallinckrodt Professor and head of the Department of Pathology & Immunology. “We have risk predictors that tell us which population is more likely to progress to more advanced stages, but we lack the ability to predict individual patient outcomes. Our study is an indication that AI methods may be able to make meaningful predictions that are specific and sensitive enough to impact patient management.”

Lung cancer is the leading cause of cancer death in the U.S. and worldwide. Most lung cancers are characterized as non-small cell lung cancers, which are largely, but not exclusively, caused by smoking. For early-stage cancer patients, tumors are confined to the lung, and surgery is recommended as a first line of treatment. Roughly 30% of such patients progress to advanced stages, when the cancer spreads to the lymph nodes and other organs. With the brain often affected first, such patients require additional treatments, including chemotherapy, targeted drug therapy, radiation therapy and/or immunotherapy. However, physicians have no way of knowing whose cancer will progress, so they frequently treat patients with aggressive therapies out of caution.

Cote worked with Ramaswamy Govindan, MD, the Anheuser Busch Endowed Chair in Medical Oncology and associate director of the oncology division at Washington University; Mark Watson, MD, PhD, the Margaret Gladys Smith Professor in the Department of Pathology & Immunology; and Changhuei Yang, PhD, a professor of electrical engineering, bioengineering, and medical engineering at the California Institute of Technology, to determine if AI could predict whether cancer will spread to the brain.

In diagnostic testing, a pathologist examines biopsied tissues under a microscope to identify cellular abnormalities that may hint at disease. Advanced technologies – such as AI – are being explored to replicate what a pathologist sees when making diagnoses but with greater accuracy, Cote explained.

A key question: Can AI detect abnormal features that a pathologist cannot?

The researchers trained a machine-learning algorithm to predict brain metastasis using 118 lung biopsy samples from early-stage non-small cell lung cancer patients. Some of the patients developed brain cancer during a five-year monitoring period, and some did not and were in remission. Then the researchers tested the AI method on its ability to predict brain metastasis, and to identify patients who develop no metastasis, using 40 other patients’ lung biopsy samples.

The algorithm was able to predict the eventual development of brain cancer with 87% accuracy. In comparison, four pathologists who participated in the study were an average of 57.3% accurate. Importantly, the algorithm was highly accurate in predicting which patients would not develop brain metastasis.

“Our results need to be validated in a larger study, but we think there is great potential for AI to make accurate predictions and impact care decisions,” said Govindan, who treats lung cancer patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine. “Systemic treatments such as chemotherapy, while effective in killing cancer cells, can also harm healthy cells and are not always the preferred treatment method for all early-stage cancer patients. Identification of patients who are likely to relapse in the brain may help us develop strategies to intercept cancer early in the process of metastasis. We think AI-based predictions could, one day, inform personalized treatments.”

The AI system evaluates tumors’ and healthy cells’ features, similar to how the human brain allows us to scan facial features for quick recognition of familiar faces. However, what the algorithm sees is unknown; the scientists are working to understand the molecular and cellular features that AI uses for its predictions. This knowledge could lead to the development of novel therapeutics and influence the design of imaging instruments optimized for the collection of data for AI.

“This study started as an attempt to find predictive biomarkers,” said Yang. “But we couldn’t find any. Instead, we found that AI has the potential to make predictions about cancer progression using biopsy samples that are already being collected for diagnosis. If we can get to a prediction accuracy that will allow us to use this algorithm clinically and not have to resort to expensive biomarkers, we are talking about significant ramifications in cost-effectiveness.”

# # #

Zhou H, Watson M, Bernadt CT, Lin S, Lin CY, Ritter JH, Wein A, Mahler S, Rawal S, Govindan R, Yang C and Cote RJ. AI-guided histopathology predicts brain metastasis in lung cancer patients. The Journal of Pathology. March 4, 2024. DOI: 10.1002/path.6263

This work was supported by the National Cancer Institute of the National Institutes of Health (NIH), grant numbers 5R01CA182746 and U01CA233363; Washington University in St. Louis School of Medicine Personalized Medicine Initiative; Sensing to Intelligence, grant number 13520296; and the Heritage Research Institute for the Advancement of Medicine and Science at Caltech, grant number HMRI-15-09-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Medicare approves genetic test for solid tumors

Test can quickly identify treatable cancer mutations, guide precision therapy

A genetic test that identifies cancer mutations in solid tumors and that was developed by researchers at Washington University School of Medicine in St. Louis has been approved for reimbursement by the Centers for Medicare & Medicaid Services (CMS). The test, known as GatewaySeq, identifies mutations that can be targeted with available drugs, helping advance precision medicine treatment strategies for patients with solid tumors, such as those of the lung, colon and pancreas.

GatewaySeq is the most recent genetic assessment tool developed by Washington University to receive CMS approval. Other recent such tests are ChromoSeq, which is a whole-genome sequencing test specifically for initial diagnosis of the blood cancers acute myeloid leukemia and myelodysplastic syndrome; and MyeloSeq, which is used to monitor the effectiveness of ongoing treatment for blood and bone marrow cancers, including acute myeloid leukemia, myelodysplastic syndrome and others.

Via Washington University Pathology Services, GatewaySeq testing is available at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine. With the new approval of the test, doctors across the country who provide care for Medicare patients diagnosed with solid tumors also can order the test through Washington University Pathology Services. With Medicare approval for the test, Medicare will cover the cost.

“We designed this test to return results as quickly as possible to inform initial treatment decisions for most solid tumors,” said Eric Duncavage, MD, a professor of pathology & immunology and one of the test’s developers. “The test focuses on identifying known gene mutations that can help direct treatment when a patient is first diagnosed. This panel captures all of the gene mutations an oncologist needs to form a treatment plan for a newly diagnosed patient. If there is a drug approved by the Food and Drug Administration (FDA) that targets a specific gene mutation, that gene is on our test. We want to make this as accessible as possible so that every patient gets molecular testing to guide treatment from the beginning.”

The testing will be performed by the School of Medicine’s McDonnell Genome Institute, which has extensive expertise in genome sequencing and analysis. Scientists at the Genome Institute were the first in the world to demonstrate the validity of whole-genome sequencing in identifying genetic errors responsible for the development and progression of cancer.

Gatewayseq Cmsapproval2
The GatewaySeq test identifies cancer mutations in solid tumors that can be treated with available drugs. The test is available through Washington University Pathology Services and is now reimbursed by Medicare.



The test is designed to run on minimal DNA, according to Duncavage, making it easier to get a sufficiently sized tumor sample to return accurate results. By focusing on gene mutations that are treatable with FDA-approved drugs, the researchers could make the test return results faster and more cost effectively than other genomic tests, increasing accessibility. The researchers also prioritized speed in returning results so that patients whose tumors have druggable mutations can begin targeted therapy as soon as possible. Test results are available in 10 to 14 days, but Duncavage said the team plans later this year to reduce that time to seven to 10 days.

If the GatewaySeq test doesn’t find treatable mutations, doctors have the option of ordering additional genomic test panels that include more genes but may take longer to return results. Rather than identify specific drugs, other genomic test panels that include far more genes can inform care in other ways. For example, such tests can help determine how aggressive the cancer is likely to be, which can guide choices about surgery, radiation therapy and chemotherapy.

GatewaySeq can help guide treatment because of effective drugs now available for specific mutations that are common in solid tumors. For example, in certain types of lung cancer, a sizable number of tumors have mutations in a gene called EGFR, which can be treated with widely available EGFR inhibitors. A specific mutation in another gene called KRAS that is also common in lung cancer can be targeted with a drug approved by the Food and Drug Administration (FDA) in 2021. There is also a therapy available for gene fusions — where two genes fuse together and drive cancer — in the NTRK gene. The GatewaySeq test also can identify these fusions.

“NTRK fusions are not super common, but there are inhibitors that target that mutation, and they work pretty well, so it’s important to identify those patients,” Duncavage said. “In the past, because of limitations in time and cost, we might run molecular testing for only a handful of patients with solid tumors. We focused on those who had already received standard care but their cancers had returned or progressed. It was a last-ditch effort. Today, we can run this test on everyone in advance so we can identify the best treatment strategies as early as possible.”

Some of the tumors the GatewaySeq test can be used to analyze include cancers of the lung, breast, skin, brain, thyroid, gastrointestinal tract, genitourinary tract, gynecologic tract, hepatobiliary tract, bone and soft tissue, and lymphomas.

“The development of a genetic assessment tool for solid tumors represents a major step forward in our efforts to provide the most complete and up-to-date information crucial in a precision approach to treating these cancers,” said Richard J. Cote, MD, the Edward Mallinckrodt Professor and head of the Department of Pathology & Immunology, which runs the pathology service in collaboration with the clinical sequencing laboratory at the School of Medicine’s McDonnell Genome Institute.

“These CMS approvals are a testament to the leadership of our department in developing tests that will specify the most precise treatments leading to the most optimal outcomes for our patients with cancer.”

Other co-developers of GatewaySeq include Lulu Sun, MD, PhD, an assistant professor of pathology & immunology, Drew Hughes, MD, PhD, an assistant professor of pathology & immunology, and David Spencer, MD, PhD, an associate professor of medicine and of pathology & immunology.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, 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.

Author: Julia Evangelou Strait, Senior Medical Science Writer, 314-286-0141 | [email protected]

Media Contact: James Goodwin, Associate Director of Strategic Communication, Siteman Cancer Center

314-680-8251 | [email protected]

Device for noninvasive brain biopsies via blood draw moves closer to market approval

A device aimed at enabling neurosurgeons and other physicians to perform noninvasive blood-based biopsies in adults with brain tumors has received Food and Drug Administration (FDA) “Breakthrough Device” designation. The device includes technology from Washington University in St. Louis and developed by Cordance Medical Inc., a medical device company in Mountain View, Calif.

The designation is aimed at providing patients and health-care providers with timely access to novel medical devices by expediting the review process needed to bring technology toward market approval.

The FDA distinction applies to devices that have undergone rigorous review and show exceptional promise of improved treatment or the ability to diagnose life-threatening or debilitating diseases. The technology was co-invented by Eric C. Leuthardt, MD, the Shi Hui Huang Professor of Neurosurgery at Washington University School of Medicine, and by Hong Chen, PhD, an associate professor of biomedical engineering at the university’s McKelvey School of Engineering and of neurosurgery at the School of Medicine.

Washington University recently licensed the technology to Cordance Medical. Leuthardt and Chen serve as advisers and shareholders of Cordance Medical, which is involved in commercializing the technology.

The device — called NeuroAccess — is portable and noninvasive, and it allows physicians to avoid high-risk brain surgery to obtain blood-based liquid biopsies of patients who have known or suspected brain tumors. The device uses sonobiopsy, a technique that targets the blood-brain barrier, a protective, semi-permeable membrane that prevents harmful substances in the blood from contaminating sensitive tissue in the brain. The interaction of ultrasound and microbubbles causes the blood-brain barrier to open temporarily so RNA, DNA and proteins from the brain can diffuse into the blood.

“The sonobiopsy approach is a revolution in brain diagnostics,” said Leuthardt, also a professor of biomedical engineering, of mechanical engineering and of neuroscience. “Just as magnetic resonance imaging (MRI) transformed how we look at the anatomy of the human brain, sonobiopsy will transform how we examine the brain on a molecular level. Essentially, we’re doing a brain biopsy without the high risks of brain surgery.”

The researchers published a study in September, in the journal NPJ Precision Oncology, that found sonobiopsy was feasible and safe for use in people.

“The breakthrough designation is the success of a team that spans numerous disciplines ranging from medicine, engineering, genetics, neuroscience and entrepreneurship to bring this concept from a very basic scientific model to an ongoing clinical trial,” Leuthardt said. “This is a triumph of collaboration.”

Said Chen, also a professor of radiation oncology and of radiology: “Sonobiopsy is poised to open doors to diagnose brain diseases in which surgical biopsies are often not an option. The technology presents new opportunities in the diagnosis of neurodevelopmental, neurodegenerative and psychiatric disorders.”

Leuthardt is the director and Chen is a member of the Division of Neurotechnology in the Department of Neurosurgery, which focuses on multidisciplinary research to create innovative engineered solutions that can be translated to patients with neurologic diseases. Washington University owns a patent on the sonobiopsy technology.

*Originally published by Washington University School of Medicine.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, 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.

Comprehensive Head & Neck Tumor Center established at Siteman Cancer Center

Washington University School of Medicine in St. Louis and Barnes-Jewish Hospital, a member of BJC HealthCare, have established a comprehensive Head & Neck Tumor Center, a collaborative, multispecialty practice of Washington University physicians and researchers whose mission is to provide cutting-edge care for patients with head and neck cancers as well as benign tumors and masses of the head and neck. Among the first of its kind in the country, the Head & Neck Tumor Center emphasizes individualized, patient-centered care with complementary research programs that have the potential to transform patients’ treatment and improve their outcomes.

Based at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, the center is co-led by three Washington University physicians: Sidharth V. Puram, MD, PhD, an associate professor of otolaryngology — head & neck surgery; Douglas R. Adkins, MD, a professor of medicine in the oncology division in the Department of Medicine; and Wade L. Thorstad, MD, a professor of radiation oncology in the Department of Radiation Oncology.

Siteman Cancer Center is a National Cancer Institute (NCI)-designated Comprehensive Cancer Center. Siteman is Missouri’s only NCI-designated Comprehensive Cancer Center and the state’s only member of the National Comprehensive Cancer Network.

“We are at a critical crossroads in the treatment of head and neck tumors,” said Puram, also chief of head & neck surgery in the Department of Otolaryngology — Head & Neck Surgery at Washington University. “As these tumors continue to become more common, we are developing newer and more advanced technologies to better manage and treat them. We are constantly improving techniques to minimize the side effects of surgery and radiation, for example, while maximizing patients’ ability to go about their normal lives after treatment. This new center will help us integrate the wide-ranging expertise that is critical to providing the best possible care for these patients.”

The new center is timely, as diagnoses of head and neck cancers are on the rise for multiple reasons — in large part, due to the increasing incidence of human papilloma virus (HPV) infection, which is sexually transmitted and a known cause of these cancers. Smoking and alcohol exposure also increase the risk of developing head and neck cancer.

“Our clinicians and researchers at the Head & Neck Tumor Center are dedicated to the development of new treatments that have the potential to improve outcomes and quality of life for patients with tumors of the head and neck,” said Timothy J. Eberlein, MD, director of Siteman Cancer Center, and the Spencer T. and Ann W. Olin Distinguished Professor. “The leaders of this center are committed to excellence in patient care and research, and this new center will provide multi-disciplinary teams to deliver outstanding care, giving hope to patients and their families.”

The center’s team will include physician specialists in otolaryngology, medical oncology, radiation oncology, neurosurgery, ophthalmology, vascular surgery, thoracic surgery, plastic surgery, palliative care, endocrinology and radiology.



“The Head & Neck Tumor Center brings together a team of experts dedicated to providing extraordinary care to every patient,” said John Lynch, MD, president of Barnes-Jewish Hospital. “Thanks to collaboration between Washington University School of Medicine and BJC HealthCare, Siteman Cancer Center is able to deliver the latest innovations and treatments, as well as pursue groundbreaking research that will impact cancer care for generations to come.”



The center will emphasize equitable access to care for all patients, whether from under- or well-resourced communities. As part of that commitment, the Head & Neck Tumor Center employs patient navigators to provide support and guidance to patients as they manage the complexities of the treatment regimens for these tumors.

Patients at the center will have the opportunity to participate in clinical trials of investigational therapeutics for head and neck cancer at Siteman, including major national or international trials.



The center’s experts are leaders in innovative surgical techniques, including robotic surgery, minimally invasive surgery, and advanced plastic and reconstructive surgery. If patients give permission, the center will sequence the genetic material of their tumors to uncover and profile the unique genetic errors and changes in gene expression that may contribute to head and neck tumors. Researchers also can analyze the immune profile of the tumor to determine if it might be susceptible to new treatments such as immunotherapy or targeted therapy. Although using these approaches in the clinical setting is still a developing area of work, such information eventually could assist in making treatment plans for individual patients and lead to entirely novel avenues of research aimed at finding new and better ways to treat head and neck tumors.



Tumors of the head and neck comprise a wide variety of conditions, both benign and cancerous. The center will provide multidisciplinary care for oral cavity tumors of the mouth and lips; throat cancers; tumors of voice box, nasal cavity, and sinuses; salivary gland tumors; thyroid and parathyroid masses and tumors; skin cancers of the head and neck, including melanoma, basal cell carcinoma, squamous cell carcinoma and others; tumors of the nasopharynx, skull base, esophagus, and eye; and rare head and neck sarcomas and lymphomas.



The locations of head and neck cancers often mean the tumors themselves as well as the therapies used to treat them can cause long-term and sometimes permanent changes to a patient’s appearance and facial movements as well as to speech, the ability to swallow, and the senses of taste, smell, hearing and vision. Because these types of changes can influence core aspects of identity, the center includes experts who can help patients navigate these kinds of challenges after treatment. Such specialists include psychologists, social workers, dentists, oral surgeons, prosthodontists, speech pathologists and nutritionists.



To make an appointment at the Head & Neck Tumor Center or to refer a patient, please contact the Siteman Patient Care Coordination Center at 1-800-600-3606 toll-free from 8 a.m.-4:30 p.m. CT weekdays, or request an appointment from our care coordinators.

*Originally published by Washington University School of Medicine.

Study reveals how treatment-resistant prostate cancer provides its own hormonal fuel

A new study in mice, led by researchers at Washington University School of Medicine in St. Louis, explains how prostate cancer senses a drop in testosterone levels due to common anti-hormone therapy and then begins making cholesterol — a necessary precursor to testosterone — to generate its own testosterone to fuel tumor growth. The study also points to a possible drug combination that may stop the cancer from feeding its own growth.

Healthy prostate cells do not produce testosterone, so the research provides long-sought answers to questions about how prostate cancer cells adapt to testosterone-deprivation therapy, a common therapeutic option, by developing an ability to supply their own hormonal fuel. Further, the research reveals that treating these aggressive prostate tumors with inhibitors that block aspects of the hormonal fuel supply chain slows tumor growth in mice. These findings suggest a novel treatment strategy for prostate cancer that has become resistant to the common anti-testosterone therapy abiraterone.

The study appears June 9 in the journal Nature Communications.

The study also may help explain why Black men are at higher risk of developing prostate cancer and tend to develop more aggressive forms of the cancer than white men of European ancestry.

“We’ve known for a long time that androgens, or male hormones such as testosterone, fuel prostate tumors — and we have drugs to treat prostate cancer that block the body’s ability to make testosterone,” said senior author Nupam Mahajan, PhD, a professor of surgery in the Division of Urologic Surgery. “But after about a year, these drugs stop working, and the androgen levels rise again. Where is this androgen coming from? Turns out, prostate cancer cells have learned a new trick; they start producing more cholesterol, which they divert to generate their own androgen. Our study shows how to block this, revealing a possible drug combination that could stop prostate cancer from fueling its own growth.”

Mahajan is also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The study demonstrated how the prostate cancer cells first detect that androgen levels have dropped. The researchers found that a key protein called SREBF1, when bound to the androgen receptor, acts as an androgen sensor. When androgen levels are low, this protein enters the cancer cell nucleus, recruits an enzyme, GCN5, to modify proteins called histones through a process called acetylation. This epigenetic modification activates many genes important for manufacturing cholesterol and lipids. According to Mahajan, these two molecular events allow the cells to make enormous amounts of cholesterol, a necessary precursor for testosterone.

“The cancer cells essentially load up the tumor with cholesterol and use that cholesterol to churn out more testosterone,” Mahajan said. “That’s the trick. They overload the prostate with cholesterol, and the normal systems for making androgen from cholesterol just work as they typically would, making drugs like abiraterone ineffective.”

Mahajan and his colleagues experimented with two inhibitors that block the molecular events that they found to be responsible for the massive cholesterol manufacturing. They used these inhibitors to treat mice that had prostate tumors that had been sampled from human patients.

One drug is afatinib, an EGFR inhibitor approved by the Food and Drug Administration to treat certain types of lung cancer. The second drug is a GCN5 inhibitor. GCN5 inhibitors have not yet made it into clinical trials, but Mahajan said there is great interest in developing this class of drugs, which could have an effect on gene regulation, cell growth and inflammation. Mice treated with a combination of these two inhibitors showed large reductions in tumor volume compared with mice treated with placebo or the anti-testosterone drug abiraterone alone.

The study also suggests that the cholesterol abundance in aggressive prostate cancer may shed light on racial disparities seen in this tumor type. The researchers found evidence that the lipid profile of prostate cancer in African American men resembles the lipid profile of treatment-resistant prostate cancer identified in this study. In other words, for reasons that remain unclear, African American men with prostate cancer appear to be more prone to having an abundance of cholesterol in their tumors than white men with the same tumor type.

“This is preliminary data, so we need to verify it in larger studies,” Mahajan said. “But our study suggests that this cholesterol profile may play an important role in African American patients with prostate cancer. African American men are at higher risk of prostate cancer, are diagnosed at earlier ages, and now we see that the kinds of cholesterol molecules that are generated in their cancers are similar to what we see in this overactive cholesterol manufacturing pathway. Their cancers are more likely to already be making these lipids, even before beginning anti-testosterone treatment.”

“We are hopeful this study will provide a solid rationale for undertaking a clinical trial of these two inhibitors combined — to block this cholesterol pathway — in patients with treatment-resistant prostate cancer,” Mahajan added.


*Originally published by Washington University School of Medicine.

Siteman Cancer Center ranked No. 10 among U.S. cancer centers

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine has been named No. 10 among cancer centers nationally by U.S. News & World Report. The recognition is part of the overall ranking of Barnes-Jewish and Washington University, which are No. 11 on the news magazine’s 2022-23 “Best Hospitals” list, released today.

Siteman was named No. 10 in cancer care, based on a review of 914 hospitals. Health-care facilities are chosen largely on patient outcomes and other data and a national survey of physicians.

In addition to their national rankings, Siteman and Barnes-Jewish each were ranked No. 1 in the St. Louis region and No. 1 in Missouri in their respective categories.

“We are honored to be named in the top 10 cancer programs in the country,” said Siteman director Timothy J. Eberlein, MD, the Spencer T. and Ann W. Olin Distinguished Professor and Senior Associate Dean for Cancer Programs at Washington University School of Medicine and BJC HealthCare. “This recognition is proof of our commitment to providing world class care to our patients every day. At Siteman Cancer Center, we pride ourselves in delivering the most cutting-edge technologies and treatments through innovative clinical trials at one of the top cancer research programs.”

Siteman is Missouri and southern Illinois’ only NCI-designated Comprehensive Cancer Center and the only cancer center in that area to be nationally ranked by U.S. News & World Report. Since 2015, Siteman also has held NCI’s highest possible rating, “Exceptional.”

Siteman Cancer Center is one of the five largest cancer centers in the country based on the number of patients treated – 70,000 people each year, including 12,000 who are newly diagnosed. Care is provided at six locations in the St. Louis region: on the Washington University Medical Campus and at Northwest HealthCare, part of Christian Hospital; Barnes-Jewish St. Peters Hospital; Barnes-Jewish West County Hospital; Siteman Cancer Center-South County; and Memorial Hospital East in Shiloh, Ill. Siteman also partners with Siteman Kids at St. Louis Children’s Hospital in the treatment of pediatric patients. The facilities all are affiliated with BJC HealthCare and staffed by Washington University physicians. The Washington University School of Medicine is a leader in medical research, teaching and patient care, and currently is No. 4 in research funding from the National Institutes of Health (NIH).

Barnes-Jewish Hospital and its Washington University physician partners also are part of U.S. News & World Report’s elite honor roll of the country’s top 20 hospitals that excel in complex specialty care.

The 2022-23 “Best Hospitals for Cancer” list is available at https://health.usnews.com/best-hospitals/rankings/cancer.