Project title: Evaluating Associations of Rurality and Neighborhood Disadvantage with Racial
Disparities in Breast Cancer Mortality Among Women in the State of Alabama

Aneja’s project will examine the role of rurality and neighborhood disadvantage in racial disparities in breast cancer mortality between Black and White patients in Alabama. Neighborhood disadvantage comprises detrimental aspects of a neighborhood that influence health and will be measured using the area deprivation index: a composite measure of neighborhood disadvantage calculated using 17 US census indicators, including poverty, income, education, employment and housing quality.

This project aims to improve our understanding of how neighborhood disadvantage interacts with individual-level factors to drive racial disparities in breast cancer outcomes by evaluating the association between neighborhood disadvantage and breast cancer mortality in Black and White patients in Alabama and the effect of rural versus urban residency on racial disparities in breast cancer mortality. Additionally, Aneja’s project aims to develop an interpretable machine learning model that integrates neighborhood-level and individual-level data to predict breast cancer mortality, which can inform community-level approaches to mitigate these disparities.

Project title: Predicting the Risk of Heart Failure in Breast Cancer Survivors

Doxorubicin chemotherapy, HER2-targeted therapies (Herceptin) and radiation are the mainstay of breast cancer treatment, but all three can lead to heart failure and premature death. Cardiovascular disease is the leading cause of death in breast cancer survivors, but there is limited information regarding heart failure in breast cancer survivors in the real-world setting.

In this study, Bhatia proposes to identify breast cancer patients at highest risk for treatment-related heart failure from the UAB Next Steps Breast Cancer Survivorship Clinic cohort and develop a risk prediction model that includes clinical and genetic information. Bhatia’s proposal is innovative in harnessing concepts from genetics and cancer survivorship and applying them to develop a risk prediction model that will allow for future risk-informed personalized management of patients at highest risk of heart failure.

Project title: Genetic Biomarkers for Therapy with NRF2 Inhibitors

Resistance to chemotherapy is commonly observed in breast cancers, leading to treatment failure and patient death. Dutta’s study will analyze the gene expression pattern of cancer cell lines that have well characterized patterns of response to drugs to identify RNA-based biomarkers for therapy resistance and explore ways to restore sensitivity to therapy.

Project title: Targeting CSF1R/PU.1Signaling and PU.1 Superenhancer Regulation in Tumor
Progression and Metastasis Across Breast Cancer Subtypes

Macrophages are normal cells in the body that, when in tumors (tumor-associated macrophages, TAMs), help drive tumor growth. We have found that the protein PU.1 controls TAM function, both as part of the colony-stimulating factor 1 (CSF1) receptor/PU.1 signaling pathway and PU.1’s regulation of genes by its interaction with highly active areas of the genetic sequence called superenhancers. In this study, Hildreth will target both ways PU.1 regulates TAM function using small molecule inhibitors and microparticle-mediated drug delivery systems in mouse models of primary breast cancer tumors across the sprectrum of breast cancer subtypes.

Project title: Hijacking Axonogenesis to Promote Breast Cancer by a Subset of Regulatory T
Cells

It is appreciated that the nerve growth into the tumor promotes breast cancer, and yet the underlying mechanisms remain obscure. Leavenworth’s proposal investigates how this process is modulated by a type of cells from our immune system. Findings obtained from the study will open a new avenue of investigation in the field of breast cancer research and formulate new therapeutic approaches to treat this most prevalent and fatal form of cancer in women.

Project title: Unique Arteriolar Niche in Expansion of Breast Cancer Stem Cells for Metastasis

Cancer stem-like cells (CSCs), a subset of malignant cancer cells, are a key player for tumor spread to other tissues and organs (metastasis). Aberrant tumor angiogenesis, or the growth of new blood vessels in tumors, may significantly contribute to metastasis by providing a favorable vascular microenvironment for CSC expansion. However, there is a significant knowledge gap as to how vascular endothelial cells in a vascular niche regulate CSCs within the tumor microenvironment of breast cancers. Based on preliminary findings, Ren plans to study the mechanisms by which how a specific protein kinase signaling in vascular endothelial cells establishes a favorable microenvironment to promote the growth and expansion of CSCs and prepares cancer cells to spread to other organs, a deadly process in breast cancer patients.

Project title: A Novel Clinically Actionable Approach to Disable Resurgence and Metastasis of
Triple-Negative Breast Cancer

Because of the lack of targeted treatment, triple-negative breast cancer (TNBC) is challenging to treat effectively. Developing new treatment options that disable the mechanisms by which cancer cells survive cytotoxic chemotherapy could improve the outcome of TNBC. Shevde-Samant’s project will test a new approach to inhibit these survival mechanisms with the goal of killing the tumor cells and reducing metastasis.

Project title: Developing Novel AKT Degrader to Selectively Inhibit the Growth of
PI3K/AKT/PTEN Pathway Mutant Breast Cancer

The goal of Xu’s project is to study the mechanism by which a novel AKT small molecule degrader inhibits breast cancer cell proliferation and division. In addition, Xu will explore the anti-tumor immune response triggered by AKT degrader treatment. Xu believes breast cancer patients with PI3K/AKT/PTEN pathway mutations will benefit from this novel therapeutic strategy.