Breast cancer is the second most common cancer diagnosed in women in the United States after skin cancer, and women with comorbidities (the presence of more than one condition/disease) often fare worse in terms of their breast cancer. Researchers believe that comorbid conditions such as diabetes, obesity and metabolic disease may alter the biology of the non-malignant cells of the tumor microenvironment and may promote progression.
Boston University School of Medicine (BUSM) researchers Gerald Denis, PhD, Andrew Emili, PhD, and Stefano Monti, PhD, together with Beth Israel Deaconess/Harvard Medical School researcher Senthil Muthuswamy, PhD, have been awarded a five-year, $2.5 million National Cancer Institute UO1 grant to develop and analyze breast tumor organoids (models). Specifically, the award will support their project: Multiscale analysis of metabolic inflammation as a driver of breast cancer.
According to the researchers, the patient population at most safety-net hospitals often presents not just with invasive breast cancer of a specific stage and molecular subtype, but also with comorbid conditions such as Type 2 diabetes which accounts for a 40 percent worse overall survival compared to non-diabetic women.
This co-morbidity burden is disproportionately high among vulnerable cohorts, such as patients at Boston Medical Center (BMC), where it can affect half of the patient population. Unfortunately, current models of breast tumor progression and immunotherapy are based on data from metabolically healthy cancer patients, ignoring metabolic /inflammatory components of Type 2 diabetes."
Stefano Monti, associate professor of medicine and biostatistics at BUSM
"Currently, the standard of care is built on data from patients who do not have these complications, thus these patients are understudied. Our goal is to produce new models that represent women with these conditions and hopefully lead to improved outcomes in their survival," added Denis, the Shipley Prostate Cancer Research Professor at BUSM. "This project leverages the strengths of a unique trans-disciplinary team with complementary strengths in molecular oncology, organoid modeling, bioinformatics and systems biology to address a major unmet clinical need,' concludes Emili, the founding Director of the Center for Network Systems Biology at BU.
The project's other researchers are Naomi Ko, MD, MPH, a medical oncologist at BMC. Kimberly Bertrand, ScD, from BU's Slone Epidemiology Center will analyze patient clinical data for outcomes of breast cancer. Anna Belkina, MD, PhD, an expert in multi-parameter flow cytometry will focus on the T cell function of the breast cancer immune infiltrates, while Joshua Campbell, PhD, a computational biologist, will analyze single cell RNA sequencing data from the tumors, T cells and organoids.