Annual Meeting on Women’s Cancer will feature findings from Washington University physicians Matthew Powell, MD, Lindsay Kuroki, MD, and others.
Washington University clinicians and researchers at Siteman Cancer Center will highlight their work against gynecologic cancers at the Annual Meeting on Women’s Cancer, March 14-17 in Seattle.
Hosted by the Society of Gynecologic Oncology (SGO), the conference convenes multidisciplinary expertise in the treatment of cervical, ovarian, endometrial and other cancers.
Presenters include:
Matthew Powell, MD, the Ira C. and Judith Gall Professor of Obstetrics and Gynecology at Washington University, who will discuss findings of the phase 3 ENGOT-OV43/GOG-30 clinical trial for advanced nonmutated epithelial ovarian cancer.
Lindsay Kuroki, MD, associate professor of obstetrics and gynecology and associate director of the Division of Gynecologic Oncology. She will discuss research focused on high-intermediate and high-risk early stage endometrial cancers.
Learn more on the Siteman and meeting websites. Follow the meeting on Facebook, LinkedIn, Twitter and Instagram using #SGOMtg #AM25IMPACT #SGO2025.
They are advancing cellular and gene therapies through numerous studies across various subspecialities, sharing their research and clinical findings related to in vivo gene therapy, CAR T-cell therapy, stem cell transplantation and more. In total, affiliated clinicians, researchers and administrators are involved in 17 presentations.
Better understanding how myelodysplastic syndromes (MDS) develop
Identifying a treatment for a broad range of myeloproliferative neoplasms (MPNs) independent of individual mutations
Improving outcomes for brain tumors in children
The projects will benefit from $1.89 million in new grants awarded through the Siteman Investment Program. The goal of the grants is to support and accelerate the pace of innovation in cancer research. The money awarded comes from a variety of sources: Pedal the Cause annual bike event and Illumination Gala through the Cancer Frontier Fund at The Foundation for Barnes-Jewish Hospital; the Cancer Center Support Grant (CCSG) from the National Cancer Institute; the Alvin J. Siteman Cancer Research Fund; the Siteman Discovery Fund; Swim Across America – St. Louis; and various philanthropic gifts via Siteman Cancer Center.
This grant cycle also includes a new clinical trial focused on a combination immunotherapy treatment for metastatic castrate-resistant prostate cancer that will expand the horizons for improved understanding of how the immune system responds to and may guide treatment of this disease.
The funded research projects are described below.
New Clinical Trial Category
Project Title: A Phase Ib Study Evaluating the Safety and Tolerability of Sipuleucel-T (Sip-T) in Combination with an N-803 in Patients with Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
Goal: To determine the recommended phase 2 dose of an immunotherapy treatment for metastatic castrate-resistant prostate cancer that combines a protein called N-803 with a Food and Drug Administration (FDA)-approved cellular immunotherapy called sipuleucel-T (Provenge). Researchers hypothesize that the combination will have an acceptable safety profile and will be feasible to administer in this population.
Project Summary: Immunotherapy is an emerging treatment platform for cancer patients that can be highly effective. However, only a subset of patients demonstrates long-term responses. A persistent challenge has been how to identify patients that would benefit, and how to enhance immunological treatments to benefit more patients. This proposal addresses these critical issues by:
Combining two immunotherapies that the researchers have shown work together in preclinical models
Advancing a promising functional scanning technology to noninvasively characterize the immune response in these patients
Prostate cancer is the second most diagnosed cancer in males. Surgery or radiation can be curative when treated early and localized to the prostate; however, it is incurable once it has spread. Novel modes of treatment are needed. The researchers propose to combine Sipuleucel-T, an FDA-approved adoptive cell therapy for prostate cancer with modest outcomes, with N-803, an immunostimulatory engineered protein that binds to interleukin-15, a cytokine involved in activating immune cells. N803 has recently been FDA-approved for bladder cancer. The researchers will establish optimal dose and schedule for this new combination approach across three treatment cohorts. They will study the immune responses in blood, and use novel, functional noninvasive imaging of the active immune system using a novel radiotracer (specific for an immune mediator called granzyme-B). Together, this work is immediately impactful to men with prostate cancer and expands the horizons for the improved understanding of how the immune system responds to and may guide treatment.
Pre-R01 Category
Project Title: Mechanisms Driving Obesogenic Diet-accelerated Gliomagenesis in NF1
Goal: To improve the outcomes for brain tumors in children. This proposal aims to determine how different dietary components (fat and sugar) affect tumor formation, epidermal growth factor (EGF) levels and epidermal growth factor receptor (EGFR) signaling in a murine model of pediatric brain tumor formation, and then to determine whether inhibition of EGFR prevents diet-accelerated tumor formation in this model. This information will be used to improve dietary counseling in patients and to design subsequent studies testing the benefits of risk-adapted therapeutic strategies in children with brain tumors and poor dietary exposure.
Project Summary: As we enter into an era of precision pediatric oncology, it is becoming increasingly important to identify the factors that underlie the risk of brain tumor development. This challenge is particularly relevant for individuals with cancer predisposition syndromes like NF1, where 15-20% of children born with a germline NF1 gene mutation develop optic pathway gliomas (OPGs). Our inability to provide accurate risk assessment information for these young children leads to frequent sedated neuroimaging, suboptimal visual screening and delays in instituting treatment for those at greatest risk. The researchers recently performed pre-clinical studies that found exposure to an unhealthy, obesity-promoting diet (obesogenic diet, Ob) increased the likelihood of OPG development in NF1 mouse models. They also identified that these animals have much higher levels of epidermal growth factor (EGF) in their blood. Based on these observations, as well as findings that a high-fat diet drives tumor formation in other tumor types through activation of the EGF receptor (EGFR), the researchers hypothesize that high dietary fat intake drives NF1-OPG formation through increased EGFR signaling. In this grant, they propose to perform a detailed analysis of how different diets (high-fat, high-sugar or high-fat, high-sugar) affect NF1-OPG formation and how this correlates with circulating EGF levels. They will then inhibit EGFR through genetic and pharmacologic means in Ob-diet-driven NF1-OPG to determine whether this impairs tumor formation. Taken together, these experiments will determine how dietary composition affects tumor formation and the role of EGF in this process. This will provide a foundation for future investigations to determine whether EGF may be used as a biomarker to detect children at higher risk of NF1-OPG due to dietary exposure and to ascertain whether EGFR-directed therapy could be a useful addition to the existing treatment strategy of NF1-OPG in children with poor diets.
Project Title: Enhancing CAR T-cell Therapy for Diffuse Large B-cell Lymphoma
Goal: To improve anti-CD19 chimeric antigen receptor T cell (CART19) therapy for patients with relapsed or refractory large B-cell lymphoma (r/r LBCL). Currently, long-term disease-free survival with commercial CART19 in r/r LBCL is only about 40%, so more strategies to improve the efficacy of CART19 are warranted.
Project Summary: Diffuse large B-cell lymphoma (DLBCL) is a common type of fast-growing non-Hodgkin lymphoma. In about 33% of patients, DLBCL returns after the first treatment (relapsed DLBCL), or the first treatment is not effective and the patient is not cured (refractory DLBCL). The FDA has approved three chimeric antigen receptor T-cell (CAR-T) therapies for use in adults with relapse or refractory DLBCL. T cells are a part of the immune system and help protect the body from infection and cancer. CAR-T therapy involves engineering healthy T cells to attack cancer cells. Unfortunately, about 50% of patients treated with CAR-T cells will relapse again with DLBCL within eight months. Interleukins are a type of protein that help activate our immune system to fight infections and cancer. Three interleukins named IL-7, IL-15, and IL-21 are especially effective at helping T cells survive, proliferate and kill infected cells. In this proposal, the researchers are testing if IL-7, IL-15 and IL-21 can help CAR-T cells kill DLBCL. Since interleukins are very short-lived and only last for one to two hours, they are testing novel long-acting versions of IL-7, IL-15 or IL-21 that last two to three days in humans. In part 1 of their proposal, the researchers are performing a clinical trial to determine if a drug named NT-I7, which is a long-acting version of IL-7, is safe and effective in helping CAR-T cells kill DLBCL tumors. In part 2, they are testing a new compound named HCW9206 that merges IL-7, IL-15 and IL-21 into a single long-acting drug. Their studies with HCW9206 will test its safety and ability to help CAR-T cells kill DLBCL in mice.
Project Title: Targeting Myeloid-biased Multipotent Progenitor to Rebalance Lineage Output in MPNs
Goal: To identify a treatment for a broad range of myeloproliferative neoplasms (MPNs) independent of individual mutations. This project will focus on cells called multipotent progenitor 3 (MPP3), the expansion of which are common in a range of MPNs, and will investigate whether the process of controlling MPP3 blood cell production mechanisms can be targeted to regulate the excessive production of myeloid cells and form the foundation of a future therapy.
Project Summary: Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by too many white blood cells, red blood cells or platelets in the bone marrow. There are several well-known disease-causing mutations, and researchers have targeted these mutations to develop treatments. Although targeted therapies have revolutionized MPN treatment, they are not curative in most cases as the mutant cell population driving disease development and recurrence is usually not eradicated. However, their success in controlling disease development and progression has shown the clinical importance of normalizing blood production in disease contexts. Additionally, there are patients without known driver mutations, with no targetable driver mutations or who develop resistance to targeted therapies. Therefore, a better understanding of the mechanisms underlying myeloid cell expansion, a shared feature of various MPNs, is necessary to develop new treatments to be used in combination with current targeted therapies or as alternatives for patients who are ineligible for current therapies. The goal of this study is to find a treatment that is applicable to a broad range of MPNs independent of individual mutations. The researchers’ previous work found there is a specific immature bone marrow population, called multipotent progenitor 3 (MPP3), that can generate white blood cells, red blood cells and platelets. Importantly, MPP3 is expanded in various MPN mouse models regardless of their driver mutations. Interestingly, distinct MPP3 subsets are specifically increased corresponding to the overproduced mature cell types in MPNs. This indicates that controlling the production of different MPP3 subsets can regulate disease development and progression irrespective of disease-causing mutations. For this project, the researchers propose to study two commonly dysregulated pathways in human blood malignancies to control the production of distinct MPP3 subsets. Their study will provide insights into the common mechanism underlying MPN development and foundations to develop broadly applicable therapeutic interventions.
Project Title: Targeting HOXB13-mediated Immune Suppression of Prostate Cancer
Goal: To demonstrate that a protein called HOXB13 can be targeted to treat prostate cancer with novel combination therapies. The study will benefit African American patients expressing increased HOXB13 through genetic and epigenetic mechanisms.
Project Summary: Prostate cancer disproportionately affects African American men compared to white men. Recently, a HOXB13 variant (X285K) predisposing to prostate cancer in men of West African ancestry was reported in a large-scale germline genetic testing. HOXB13-X285K was significantly enriched in self-reported Black (1.01%;~21000 men screened) versus white (0.01%) patients. HOXB13-X285K carriers tended to have more aggressive disease, due to increased protein stability that resulted in an increase in cell proliferation. Besides germline mutations, gain-of-function modification in HOXB13 bump up HOXB13 RNA and protein levels. Thus, screening for HOXB13 expression and development of effective treatments is critical to improve clinical outcomes. Prostate-Specific Membrane Antigen-Targeted Imaging (PSMA-PET) imaging could be combined with molecular profiling of prostate biopsies for HOXB13 expression in white and African American patients for early detection and treatment of aggressive prostate cancers.
Results from this study will reveal previously unknown epigenetic regulation of immune suppression in prostate cancer. The researchers’ pre-clinical studies will advance the use of other checkpoint inhibitors alone or in combination with PD-L1/PD-1 axis to overcome poor response to immunotherapy. The results will provide the basis for combination therapies to improve treatment outcomes for prostate cancer patients.
Project Title: Regulation of Hematopoietic Stem Cell Metabolism by Stathmin 1
Goal: To determine how the gene called Stathmin 1 (Stmn1) regulates hematopoietic stem cell (HSC) metabolism and contributes to hematopoietic malignancies, especially leukemia. The researchers predict that high levels of Stmn1 support the needs of growing leukemic cells, and that it may be a new therapeutic target on which to focus.
Project Summary: The gene stathmin 1 (Stmn1) is expressed at high levels in normal blood stem cells and is overexpressed in blood cancer cells. The researchers’ preliminary studies suggest that Stmn1 is important for supporting various aspects of healthy blood stem cell metabolism, including maintaining healthy mitochondria and protein turnover in the cell. They predict that high levels of Stmn1 in leukemia cells are necessary to sustain the unique metabolic needs of leukemia cells. The proposed studies will determine the mechanisms by which Stmn1 influences blood stem cell metabolism, and in future studies researchers will determine whether inhibition of Stmn1 impairs the growth of leukemic blood cells. Ultimately, these studies will test Stmn1 as a novel therapeutic target to treat leukemia. As Stmn1 is overexpressed on multiple types of blood cancers, and loss of Stmn1 in mouse models has few effects outside of the blood system, the researchers predict that Stmn1-directed drugs could be useful to treat a wide variety of leukemias with limited side effects.
Project Title: Defining How the Role of DDIT4 in Mitochondrial Metabolism and Turnover Impacts Chemotherapy Responses in Acute Myeloid Leukemia
Goal: To identify molecular pathways that support chemotherapy resistance in acute myeloid leukemia (AML) and utilize that information to identify potential new therapeutic targets. This proposal will specifically focus on a protein called DNA-Damage Induced Transcript 4 (DDIT4) that the researchers hypothesize supports AML cell survival and chemotherapy resistance and will establish that targeting this protein in a certain pathway will have therapeutic potential for leukemia patients.
Project Summary: Annually, approximately 1 in 12,500 Americans are diagnosed with acute myeloid leukemia (AML), and more than 12,000 die from the disease. The overall survival rate of AML patients is below 25% for adults and 70% for children, and these poor outcomes are largely due to high rates of resistance to the current standard-of-care treatments and disease relapse. The researchers have discovered that a protein called DDIT4 (DNA-Damage Induced Transcript 4) may play a central role in how AML cells evade current chemotherapies. This project will decipher the molecular mechanisms by which DDIT4 promotes chemotherapy resistance as well as test whether pharmacological targeting of DDIT4 enhances the anti-leukemia effects of current chemotherapies.
Project Title: Rescuing BRCA1 Haploinsufficieny and DNA Replication Fork Stability with Antisense Oligonucleotides
Goal: To study early detection strategies for breast and ovarian cancer in women with BRCA1 or BRCA2 gene mutations and research molecularly guided and nonsurgical interventions to prevent tumor development.
Project Summary: More than 1 in 500 women are affected by mutations in the breast cancer susceptibility genes BRCA1 or BRCA2. While it is known that these women have up to an 80% risk of developing breast and ovarian cancer in their lifetime, exactly why these cells become cancerous is unknown. The only preventive options currently available are risk-associated prophylactic surgeries of ovary/fallopian tube and breast removal, which result in surgical menopause and significant aesthetic consequences. Therefore, two major challenges that women with BRCA1 or BRCA2 gene mutations currently face are the lack of:
Early detection strategies to identify which carriers will develop these malignancies
Molecularly guided and nonsurgical strategies to prevent breast and ovarian tumor development
This project joins experts in DNA replication (Alessandro Vindigni, PhD), RNA processing (Sergej Djuranovic, PhD), and ovarian cancer (Mary Mullen, MD, MSCI) to tackle these challenges. The researchers know that BRCA1 is important for DNA replication and it helps protect the genome. Women with mutations in the BRCA1 gene have less BRCA1 protein in their cells. The researchers believe this lack of BRCA1 protein causes problems with DNA replication. These problems lead to more mutations in the genome, which can cause cells to become cancerous. They will test these new ideas using fallopian tube cells, new technologies from the Vindigni lab, and samples from patients. Next, they will use a technology developed by the Djuranovic lab called “antisense oligonucleotides” to increase BRCA1 protein levels. The researchers think that by increasing this protein, they can stop the unstable replication forks and prevent mutations that cause these cancers. Collectively, their studies will:
Define the early changes that happen when normal fallopian tube cells with BRCA1 gene mutations turn into tumors
Establish novel nonsurgical strategies to prevent ovarian cancer development in women with BRCA1 gene mutations
Goal: To begin developing a new way to treat patients suffering from myelodysplastic syndrome, or MDS, by understanding how blood cells with mutations grow and expand. This project will test the safety and efficacy of selectively eliminating mutated blood cells by hyperactivating a pathway that reduces their growth, which could improve patients’ lives.
Project Summary: Myelodysplastic syndromes (MDS) are one of the most common types of blood cancer in adults. MDS patients suffer from problems related to low blood counts, including life-threatening infections and bleeding. Once MDS develops, the only cure is a bone marrow transplant. However, most patients are not eligible for a transplant due to their advanced age and other illnesses. Understanding how MDS develops may help researchers identify new ways to treat patients with MDS.
Up to half of MDS patients have mutations in genes in their blood cells that regulate how RNA is stitched together in a cell, called RNA splicing. A goal of this project is to understand how blood cells with a gene mutation that controls RNA splicing grow, expand and cause MDS. The researchers observed that early after a cell gets an RNA splicing gene mutation, mutant cells grow slower than normal cells. However, over time, a mutated cell changes and outgrows normal cells, causing MDS and other blood cancers. The researchers are studying what happens early after a mutation occurs in a blood cell so they can identify ways to kill cells with the mutation.
Their initial studies identified a pathway in mutant blood cells that they can hyperactivate to preferentially kill mutated cells in a culture dish. The researchers now want to test if they can kill mutant cells in preclinical models and see if it is safe. If this works, they could design a trial to test if a new approach could kill mutated MDS cells in patients and improve their lives.
More than 2 million people will be diagnosed with non-melanoma skin cancer in the U.S. this year, according to the American Cancer Society. USA Today highlighted signs to look for and spoke with Washington University medical oncologist Alice Zhou, MD, PhD, at Siteman Cancer Center about those at risk.
Srikanth Singamaneni, PhD, the Lilyan & E. Lisle Hughes Professor at the McKelvey School of Engineering
They are among the162 new senior members who will be inducted at the NAI’s annual conference in June.
Aaron DiAntonio, MD, PhD
Aaron DiAntonio, MD, PhD
DiAntonio is being recognized for outstanding contributions to the field of neuroscience, especially for showing how nerves respond to injury and disease and for developing ways to protect them from degeneration.
After injury and in some diseases, axons — the long fibers of nerve cells throughout the body — spark a self-destruct mechanism that disrupts communication in the nervous system. This is common to many neuronal injuries and diseases, revealing potential for a treatment for multiple disorders.
Working with WashU’s Office of Technology Management (OTM), DiAntonio co-founded Disarm Therapeutics, a startup developing medicines to stop the loss of axons and to prevent or treat a range of diseases, which has been acquired by Eli Lilly.
John DiPersio, MD, PhD
John DiPersio, MD, PhD
DiPersio, who treats patients at Siteman, is being recognized for outstanding contributions to understanding blood cancers and for the development of new ways to improve therapies for such cancers, including leukemia and lymphoma.
His work focuses on improving stem cell transplantation and developing novel cell-based immunotherapies. Working with the Office of Technology Management, he co-founded Wugen, a WashU startup creating investigational cellular immunotherapies. He developed so-called “universal” CAR-T cell therapies, which don’t require the donor and recipient to have matching immune systems.
DiPersio is developing small-molecule drugs to help collect more healthy stem cells from donors more easily, increasing the chances for successful transplants.
Srikanth Singamaneni, PhD
Srikanth Singamaneni, PhD
Singamaneni is an international pioneer in the design, synthesis and biomedical applications of plasmonic nanostructures.
His research integrates nanotechnology and biomaterials to create innovative products with applications from diagnostics to wastewater treatment.
His lab has pioneered the design and synthesis of ultrabright fluorescence nanolabels and devised methods to preserve biomolecules under harsh conditions. He holds numerous U.S. patents and licenses the core plasmonic fluors technology to Auragent Bioscience, where he is co-founder and chief scientific officer.
Pioneering work in genetic testing at Washington University School of Medicine and elsewhere has yielded invaluable – even lifesaving – information for cancer patients and physicians. Newsweek spotlights these groundbreaking advances, including WashU’s sequencing of the first cancer genome, as well as the development of ChromoSeq, the only whole genome sequencing test approved by Medicare, by Washington University pathologist Eric Duncavage, MD, at Siteman Cancer Center.
Washington University researchers will focus on Hodgkin lymphoma, myeloma and pancreatic and head and neck cancers
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is excited to announce the next cohort of pilot projects funded by the Institutional Research Grant from the American Cancer Society. The $360,000 grant will support 12 pilot projects from 2025–2027, including the four new projects described below.
Jason Weber, PhD
Under the leadership of Jason Weber, PhD, who has been the principal investigator of the grant since 2011, these awards support independent, self-directed investigators early in their careers and enable them to conduct research in areas of special interest to the American Cancer Society.
Washington University has funded early-career oncology researchers with this grant since 1958. Learn about projects initially supported in 2022, 2023 and 2024.
Project Title: Characterizing the Expression Profile of Hodgkin Lymphoma Using Single Nuclei RNA Sequencing
Although Hodgkin lymphoma is relatively uncommon, with about 7,000-7,500 new cases diagnosed annually in the U.S., it comprises about 10% of lymphomas in the Western world. The treatment is relatively successful. However, patients who relapse or are refractory to treatment have few secondary treatment options, and overall survival remains low in this patient population. Thus, a better understanding of the pathobiology of this disease remains an important clinical question. Current genomic technologies struggle with cancers defined by rare malignant cell populations, leaving some cancer types poorly described — Hodgkin lymphoma is one such cancer. This project will address these shortfalls by using newly developed technologies and diverse sources of DNA and RNA to describe somatic variation and patterns of gene expression. Researchers will comprehensively investigate the biology of this disease to understand its etiology, with the goal of creating data that will inform new treatment strategies. Specifically, the data produced here will investigate the cells that are responsible for this disease. We will also investigate the immune environment that supports the proliferation of malignant cells. These data will provide foundational knowledge that will support our understanding of the biological processes that underlie this disease, which has the potential to create new and innovative treatment options.
Project Title: CAR T-cell Therapy with Radiation-Based Lymphodepletion for Patients with Myeloma and Advanced Chronic Kidney Disease
Multiple myeloma remains an incurable cancer, but recent advances in treatment have helped patients live longer after diagnosis. Cellular immunotherapy with genetically modified chimeric antigen receptor T cells (CAR T) has been shown in large studies to be better than standard therapies in patients whose myeloma has come back after treatment. The effectiveness of CAR T treatment depends, in part, on giving preparative, or “lymphodepleting,” chemotherapy (LDC) prior to CAR T infusion. However, patients with poor kidney function often cannot receive standard LDC, making them unable to receive CAR T therapy. In addition, poor kidney function is very common (30% to 40%) in patients with multiple myeloma and particularly in Black patients, leading to inequitable access to this lifesaving therapy. Therefore, researchers are studying new methods of LDC that are safer in patients with poor kidney function. Radiation treatment has been used as preparative treatment in stem cell transplant for decades but has not been used as LDC with CAR T. Work by the research team in the lab has shown that replacing fludarabine with total body irradiation in LDC leads to similar CAR T anti-cancer activity without causing low blood counts, suggesting this approach can be safe and effective in humans. This study proposes using radiation as part of LDC for patients with multiple myeloma and poor kidney function who would otherwise be ineligible for CAR T therapy or would be at increased risk of unacceptable side effects from standard LDC. Researchers plan to collect patient samples to better understand the changes in the myeloma and CAR T cells after using radiation in LDC. If this pilot study is successful, it will help improve access to CAR T therapy, including for patients with poor kidney function and for members of historically underrepresented groups.
Project Title: Investigating Inflammatory Crosstalk in the Pancreatic Cancer Tumor Microenvironment
Pancreatic cancer is a deadly disease for which few effective treatments are available. It is well-established that pancreatic tumors are comprised of both cancer cells and noncancerous cells that interact with one another to influence patient outcomes. This project focuses on defining how noncancerous cells contribute to cancer cell growth and resistance to treatment in pancreatic cancer. Preliminary work shows a key role for inflammatory proteins produced by noncancerous cells in supporting cancer cell growth. Using sophisticated techniques including mouse modeling of cancer and engineering of tumor cells, researchers will investigate how cellular interactions in pancreatic tumors drive cancer growth and treatment resistance. The findings from this work are anticipated to open the door to new treatments for pancreatic cancer to improve outcomes for patients.
Project Title: NRF2 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma
The introduction of immunotherapy has transformed the treatment and outcomes for many cancers and provides a potentially curative option for many patients. However, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) continues to be a devastating prognosis with limited treatment options. Despite success in similar cancers, response rates to immunotherapy in R/M HNSCC are less than 20%, with long-term control in fewer than 5% of patients. Despite much investigation, PD-L1 expression remains the only clinically utilized biomarker guiding patient treatment decisions. Retrospective human tumor studies, mouse models and the research team’s previous studies suggest that activation of the NRF2 oxidative stress pathway plays a central role in shaping the immune cells within the tumor and impairing the response to immunotherapies. In this study, the researchers will use human patient samples and their genetically engineered mouse models to explore how NRF2 pathway activation impacts the immune microenvironment and impacts immunotherapy response rates. They will also explore how a novel NRF2 inhibitor, WCDD115, enhances the efficacy of immunotherapy in mice models. They hypothesize that NRF2 drives an immune “cold” tumor with comparably fewer infiltrating cytotoxic lymphocytes and that treatment with WCDD115 will create a more immune-rich microenvironment capable of producing tumor regression when combined with anti-PD1 immunotherapy. The goal is to develop and validate a clinically useful NRF2 biomarker assay that can be translated into clinical practice to guide treatment decisions, including the use of combined immunotherapy and NRF2 inhibitors in patients with NRF2-active disease.
The National Cancer Institute, part of the National Institutes of Health (NIH), has awarded Washington University investigator Aimilia Gastounioti, PhD, at Siteman Cancer Center a five-year, $3 million grant to improve breast cancer risk assessments for Black women. Gastounioti is an assistant professor of radiology in the Computational Imaging Research Center in for Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis. This is her first R01 grant.
The project aims to address an important need for a patient population that is not well served by current risk assessment tools. Black women are slightly less likely to develop breast cancer than white women are, but their mortality rates for the disease are strikingly higher — they are 40% more likely to die from the disease than white women. The risk models that are used to identify and plan treatments for patients who may develop the disease are not well suited, and historically have been less accurate, for Black women.
New tools that provide personalized risk assessments using artificial intelligence have shown enormous promise, but so far have largely been trained on data from digital mammography of white patients. Gastounioti, a principal investigator with MIR’s Computational Imaging Research Center, and her team will develop deep learning and medical imaging informatics tools on a database of more than 95,000 digital breast tomosynthesis (DBT) exams from Black women. The database is a collaboration of WashU, Emory University in Georgia, University of Pennsylvania and Columbia University Irving Medical Center in New York. Unlike standard digital mammography, DBT captures images of breast tissue from multiple angles, resulting in more-detailed tissue representations.
The goal is to develop and distribute an accurate screening tool specific to the patient population, which has the potential to drastically improve early breast cancer detection and prevention for Black women.
Breast cancer rates are climbing for women under age 50, according to the American Cancer Society’s 2025 annual report. Washington University researchers Graham Colditz, MD, DrPH, and Adetunji Toriola, MD, PhD, at Siteman Cancer Center spoke with The New York Times about likely reasons.
Genetic information is often used to guide precision cancer treatments. In the future, genetics could guide personalized efforts to stop smoking and prevent lung cancer.
343,000+. That’s the number of cigarettes Chris Kneibert, 65, has probably smoked over his lifetime.
“I basically smoked a pack a day for 47 years,” he said. “And there are 20 cigarettes in a pack. I smoked when I woke up or when I got bored. I smoked in the mornings and socially. It seemed like the thing to do when I first went to college, and I never really stopped — or couldn’t.”
The Centers for Disease Control and Prevention estimates that 49.2 million people in the U.S. — one in five adults — use tobacco products. Add e-cigarettes/vaping, cigars and smokeless tobacco products, and the number rises. With today’s average cost of cigarettes at more than $8 per pack, that means Kneibert and other smokers dole out almost $3,000 annually to support a pack-a-day habit.
The bigger problem comes when individuals want to quit smoking. Tobacco products contain nicotine, a known addictive chemical. When people smoke, the nicotine absorbs into the bloodstream and increases dopamine levels in the brain. Smokers then start craving the “hit” of nicotine, ingesting it more and more, and rapidly become addicted. Trying to quit causes withdrawal symptoms, and about half the people who want to quit, can’t.
“I really thought I could quit on my own, but I enjoyed it too much,” said Kneibert. “Even when news came out that smoking was bad for you and could cause cancer or heart attacks and stroke, I didn’t stop. It really was an opportunity for me to step outside and smoke a cigarette and temporarily get out of whatever I was doing.”
In the 1980s, the U.S. Food and Drug Administration (FDA) approved a nicotine gum, Nicorette, as the first medication to help people quit. Over-the-counter sales of Nicorette were authorized in 1996. Along the way, a plethora of other treatments became available, including hypnosis and behavioral therapy as well as phone and web-based counseling services to support those who wanted to quit. Still, many people can’t stop smoking.
“I tried the nicotine gum and was successful for only one to two months, said Kneibert. “I was not optimistic I could succeed and stop smoking.”
Using Genetics to Quit Smoking
Last year, Kneibert was told about a new clinical trial underway at Washington University School of Medicine in St. Louis. The study focuses on gathering genetic information from individuals identified as smokers to better understand the mechanisms behind their smoking addiction as a tool for identifying optimal treatment options.
“I am very interested in how we can motivate people to have healthy behaviors,” said Washington University psychiatrist and physician scientist Li-Shiun Chen, MD, MPH, ScD, director of the Tobacco Treatment Program at Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine. “Precision medicine is used in cancer treatment but not used in cancer prevention. We wanted to know if we could use precision medicine to affect behavior and lower the risk of health problems stemming from smoking. We, therefore, could shift the paradigm from cancer treatment to potentially cancer prevention using genetics and targeted therapies.”
Two years ago, Chen, along with organizational psychologist Alex Ramsey, PhD, and their colleagues in Washington University’s Precision Prevention and Treatment Lab received grants from the National Institutes of Health to see if individualized counseling along with a personalized genetics report highlighting the percentage of cancer risk would result in more effective treatment and smoking cessation rates. The first trial, PRECISE, focused on identifying the level of risk for lung cancer and counseling on the benefits of lung cancer screening for each study participant. In the second trial, MOTIVATE, researchers added information related to genetic markers that identified optimal smoking cessation treatments for each participant.
“Like an ACT test for college, a genetics ‘score’ can tell you your own individual lung cancer risk and, significantly, how difficult it may be to actually quit smoking,” Chen said. “We analyzed DNA and created a report that not only showed the benefits of quitting smoking but, significantly, also showed which smoking cessation products might be better for a person to try based upon their own genetic profile.”
In the MOTIVATE trial, the team analyzed more than 50,000 biomarkers linked to elevated cancer risk in 100 study participants. A report then was shared with both primary care physicians and patients to see if it would motivate individuals to stop smoking.
The report identified genetic markers and noted whether a person had a high or low nicotine metabolism level. “If you have a slow metabolism, you could use an other-the-counter nicotine patch to help you quit,” Chen explained. “But if you have a fast metabolism, nicotine patches or gum are less likely to work. In those cases, individuals would be more successful if they used a prescription medication.”
For Kneibert, an early participant in the MOTIVATE trial, he had a genetic marker that pointed toward a fast metabolism. His report also showed that he had a very high risk for developing lung cancer. “It was in the red zone, which was bad,” he recalled. He agreed to try Varenicline, one of seven FDA-approved prescription medications to help adults quit smoking. To his surprise, it worked.
“I started with one pill a day and still smoked,” he said. “But when I got to two pills a day, the medicine stopped my nicotine receptors from working. I would smoke and think to myself, ‘That was very unappealing.’ I quit about a month later and I’ve been smoke-free ever since.”
Chen and her colleagues still have a long way to go before they say their research will make a huge impact in the field of cancer prevention. The MOTIVATE trial is still underway, and they plan to recruit 800 participants to continue testing whether the genetics report motivates people to change behavior, stop smoking and get regular screenings for lung cancer. Still, publication last year of their early research is gaining attention.
“I believe we are at the forefront of innovation, and Siteman Cancer Center is really leading the country by using genetics for cancer prevention,” stressed Chen. “Patients and their doctors are more motivated when we can offer evidence-based risk assessments and smoking cessation treatment suggestions. I predict that we can move the needle on effective addiction treatment and, therefore, prevent some cancers because of our work.”
Kneibert now steps outside often to enjoy nature instead of smoking a cigarette. He also got a lung cancer screening, testing negative for any cancer. “I’m glad I found out why the nicotine patch didn’t work before,” he said. “That report was eye-opening and made me want to try to quit again because it really wasn’t my lack of willpower that caused me to fail.”
“I’m proud of myself for quitting,” he added. “And my kids are proud of me, too.”
To learn more about the MOTIVATE trial call 314-273-3826.
# # #
Chen, Tony et al. Genomic insights for personalised care in lung cancer and smoking cessation: motivating at-risk individuals toward evidence-based health practices. eBioMedicine. December 2024.
