Siteman Cancer Center Announces 2025 American Cancer Society-Funded Pilot Projects

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.

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 

Principal Investigator: Felicia Gomez, PhD

Project Summary:

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

Principal Investigator: Michael Slade, MD, MSCI

Project Summary:

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

Principal Investigator: Max Wattenberg, MD

Project Summary:

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

Principal Investigator: Paul Zolkind, MD

Project Summary:

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.