The below funding round-up spotlights recently funded research led by MCW Cancer Center scientists and their lab members. Our people share why the research is critical, and the impact they intend to make to improve treatment, outcomes, and quality of life—and dismantle barriers—for patients living with cancer.
Cancer Biology
Jong-In Park, PhD, professor of biochemistry, is receiving annual funds of $289,179 for five years from the National Cancer Institute (NCI) for the project, The Role of Mortalin in Thyroid Cancer. This research aims to elucidate the mechanism by which ESRRA transcriptionally upregulates mortalin expression in thyroid cancer—the most common neoplasm of the endocrine system and the seventh most frequent human malignancy among women in the United States, with rising incidence in Wisconsin. During the study, Dr. Park and the research team will determine the role of the ESRRA-mortalin axis for tumor cell metabolism, and evaluate the potential of the metabolic processes that ESRRA and mortalin regulate as a therapeutic target.
“Despite decades of pathophysiological mechanism studies, therapeutic modality for thyroid cancer is still limited due to the heterogeneity of tumor subtypes. As such, identifying a tumor subtype-specific weakness is expected to help develop additional therapeutic strategies, which is the central focus of this project,” said Dr. Park.
Vera Tarakanova, PhD, professor of microbiology and immunology, is receiving annual funds of $150,000 for two years from the American Cancer Society for the project, The Dr. Jekyll/Mr. Hyde Nature of Host IRF-3 in Gammaherpesvirus Pathogenesis. The study builds on previous findings that IRF-3, a major antiviral host factor, is usurped by the cancer-associated Gammaherpesvirus which enables the virus to maintain its chronic infection, despite the immune system’s best efforts to combat the disease.
“The award will help us further understand how the virus subverts the major antiviral factor of the host so we can identify and target viral vulnerabilities, with the goal of improving control of viral infection and subsequent lymphomagenesis,” said Dr. Tarakanova.
Cancer Control
Chandler Cortina, PhD, MD, MS, FSSO, FACS, assistant professor of surgery, is receiving annual funds of $249,956 for two years from the Patient-Centered Outcomes Research Institute for the project, Creating a Transdisciplinary Approach to Address Transgender/Non-binary (TNB) Cancer Disparities. The project will use a collaborative, co-learning approach to build inclusive understanding of the root causes of cancer disparities in the TNB community; and elucidate potential solutions to better support patients and their providers. The team anticipates findings over the next two years will lead to more collaborative research efforts to mitigate disparities.
“Transgender and nonbinary patients are under-served by the current U.S. healthcare system and experience disparities across the cancer continuum. In addition to facing significant barriers to care, data on cancer and cancer disparities for TNB patients are critically limited; which we can solve for,” said Dr. Cortina.
Joan Neuner, MD, MPH, professor of medicine, is receiving annual funds of $167,703 for four years from the Department of Defense for the project, Chemotherapy Dosing in Patients With Obesity: Are Oncologists Optimally Balancing Risks and Benefits to Avoid Overtreatment and Undertreatment? The study aims to identify optimal chemotherapy use in patients with breast cancer and obesity. Patients enrolled in chemotherapy trials are younger, healthier, and less likely to be obese or have comorbidity than those encountered in practice, making it difficult to assess optimal dosing for a patient outside of the clinical trial population. Current dosing guidelines do not provide detail into how much to reduce most agents, nor the level of some toxicities (such as neuropathy) that should be considered “acceptable” in real-world practice. The team expects to have completed results and findings by 2026.
“Chemotherapy treatment has a narrow therapeutic index, meaning small dose changes can separate life-threatening toxicities and insufficient therapeutic effect, leading to worse outcomes. I hope this study can close the gap in understanding the balance of benefits and risks in chemotherapy, and when we need to de-escalate or not pursue medications,” said Dr. Neuner.
Discovery and Developmental Therapeutics
Michael Deininger, MD, PhD, professor of medicine, is receiving annual funds of $314,459 for four years from the NCI for the project, The Function of MS4A3 in Normal and Malignant Hematopoiesis. The research aims to uncover shared mechanisms between TKI-resistant, blast phase chronic myeloid leukemia ML (BP-CML), and persistent residual leukemia, that could lead to universal therapeutic interventions. Dr. Deininger said the study has significant potential to reshape our understanding of treatment for CML. The team has generated preliminary data and is currently in the process of establishing a mouse model.
“The identification of MS4A3 as a key player in cytokine receptor endocytosis and signaling not only advances our knowledge of hematopoiesis and leukemogenesis but establishes MS4A3 as a functional tumor suppressor. Most notably, the development and proof of concept for MS4A3 nanoparticles introduce a promising avenue for future therapeutic interventions, offering hope for improved outcomes and potentially transformative treatments for CML patients,” said Dr. Deininger.
Joseph Zenga, MD, assistant professor of otolaryngology, is receiving annual funds of $140,250 for two years from the NCI for the project, Determining the Role of the SDF-1/CXCR4 Pathway and its Intersection with Chronic Stress to Establish Novel Precision Approaches to Head and Neck Cancer Management. Head and neck cancer patients experience a high degree of stress and social isolation related to speech and swallow dysfunction that results from their disease and required treatments. Evidence suggests chronic stress may contribute to poor cancer outcomes. In this study, Dr. Zenga and the research team explore how mechanisms contribute to stress-induced cancer progression, and how one particular chemokine signaling pathway—the CXCR4/CXCL12 axis—may play into this.
“We anticipate the results of our study will inform future directions for therapy to help mitigate stress-induced cancer progression in head and neck cancer patients. Specifically, we hope that novel agents targeting the CXCR4/CXCL12 pathway will play a central role,” said Dr. Zenga.