NEWS & PROGRESS

Cancer immunotherapy activates a patient’s own immune system to recognize and kill tumor cells. However, as the tumor grows, it secretes chemicals which block the immune cells from attacking them. In addition to tumor cells, immune cells and bone corroding cells called osteoclasts in the tumor environment also respond to these chemicals and adapt themselves to helping the growing tumor contributing immune suppression and bone damage. Effective therapies to cure metastatic breast cancer should simultaneously address these pathologies. Toward this ultimate goal, we propose to test unique combination therapies that are biologically-driven and have shown promise in preliminary studies. We will adopt a genetic antibody engineering approach to establish a stable therapeutic strategy to overcome current limitations in breast cancer immunotherapy.

Understanding the impact exercise has on a cancer survivor’s gut microbiome can improve the health and well-being of cancer survivors by enhancing treatments targeting the gut microbiome. This proposal tests feasibility of a home-based, remote-only research protocol that is more accessible to cancer survivors unable to attend supervised exercise including but not limited to rural populations. This study will also determine if exercise influences the gut microbiome differently in non-Hispanic Black (NHB) compared to non-Hispanic White (NHW) breast cancer survivors.

Ionizing Radiation (IR) is an effective tool in cancer treatment that is used for the management of clinically challenging cancers such as TNBC. IR creates significant DNA damage, in particular, double strand breaks (DSB). In response to DNA damage, tumor cells launch powerful survival programs that enable repair mechanisms. We have discovered that TNBC cells launch activation of Hedgehog (Hh) signaling in response to IR. Delayed, erroneous, or incomplete repair of DSBs in rDNA loci can lead to deleterious effects and can culminate in cell death. While this aspect presents a clear vulnerability of cancer cells, how to specifically target this susceptibility to treat cancer remains largely unexplored and presents a gap.

Support from the BCRFA funds the research portion of Dr. Shinn’s surgical breast fellowship at UAB, focusing on the evaluation of high risk breast lesions.

Metastatic breast cancer (also known as stage IV or advanced breast cancer) is when the breast tumor has metastasized or spread to other organs in the body, including the lungs, bones, liver, or brain. The 5-year survival rate for women with metastatic breast cancer is 27%, causing the vast majority of deaths from this disease. We recently found a FOXP3 gene with dual roles in tumor cells and immune cells and is involved in tumor metastasis. Interestingly, FOXP3 in tumor cells stops the spread of cancer, but FOXP3 in immune cells is a metastasis promoter. We have successfully developed a new approach to activate the FOXP3 expression in tumor cells, inhibiting tumor growth and metastasis. This proposed study will develop new technology to explore the mechanism of dual roles in tumor cells and immune cells within the tumor microenvironment. We hypothesize that FOXP3 is a critical regulator in tumor-immune interaction and metastasis. First, we will investigate the mechanism of FOXP3-mediated tumor-immune interactions during metastasis in cell and animal models. Next, using our developed technologies, we will alter the FOXP3-mediated tumor microenvironment, determine the role of FOXP3 in the tumor microenvironment and metastasis, and identify distinguishing markers of tumor metastasis. Although this is basic research, our identified targets will not only help the understanding of lethal and metastatic breast cancer but also have the potential to identify new biomarkers for the early detection of lethal and metastatic breast cancer.

There is a critical, unmet, and urgent need for platforms that match tumors with effective cancer therapies prior to treatment. With BCRFA support, CerFlux is developing innovative predictive low-cost technology to bridge this gap by rapidly (7 days) matching core biopsy tissue from the patient with several therapeutics simultaneously – outside the patient, before treatment – to identify the right treatment for each patient.

The goal of this project is to develop a new class of potent anti-breast cancer analogs of Clofarabine an FDA-approved drug discovered by Southern Research for treating relapses acute lymphoblastic leukemia in children, and to determine the mechanism by which these new analogs inhibit breast cancer cell growth and proliferation.

Triple negative breast cancer spreads very rapidly and difficult to treat. However, early detection of this disease can save lives with available treatments. Our goal is to develop mitochondria based tests for early diagnosis and long-term surveillance of these women to support better living.

This project will generate basic information on the protective mechanisms of mitochondrial delivery of TAT-hOGG1 in the breast cancer progression in mouse models of breast cancer. This TAT-protein delivery based translational study will provide the basis for the new unconventional therapeutic strategies and to more effective cancer therapy. This project is particularly timely given the lack of available effective therapies and prognosis for patients with advanced breast cancer.

PARG inhibitors (PARGi) are found to work well when targeted to BRCA-mutant cancer cells but do little when treating BRCA normal or BRCA-revertant cancer cells that are also resistant to PARP-inhibitors. We find that the simultaneous administration of a PARG inhibitor (PARGi) with the NAD+ precursor dihydronicotinamide riboside (NRH) triggers near 100% tumor cell death, with no impact on non-tumorigenic cells. Our goal in this proposal will be to expand our analysis of this treatment paradigm to a large panel of breast cancer and breast normal cells to ultimately target therapy-resistant breast cancers with this ‘induced synthetic lethality’ treatment paradigm.

The process by which breast cancer cells leave the original tumor and spread to other parts of the body is called breast cancer metastasis. Metastasis is responsible for the vast majority of breast cancer-associated deaths. The goal of our work is to understand how breast cancer cells invade other organs in order to identify new therapeutic strategies to halt metastatic spread.

Funding provided by the BCRFA will establish a new research collaboration between Auburn and UAB to determine efficacy of an experimental anticancer compound, ADT-030, for the treatment of triple-negative breast cancer using a high aggressive mouse model of metastasis. ADT-030 acts by a novel mechanism to inhibit an enzyme, phosphodiesterase 10A, that drives Wnt/β-catenin transcription of proteins (e.g., MYC) essential for cancer cell proliferation and survival. The research will also determine if ADT-030 can activate mechanisms of antitumor immunity to enhance or broaden chemotherapy or immunotherapy.

A few medication treatments might help lower breast cancer risk, especially women who are at high risk. However, potential disparities in utilization of these medication treatments between Alabamian women and women in other geographic regions. This study analyzes existing data to understand whether and how the use of these medication treatments might impact overall survival among women with breast cancer in Alabama.

The Information is Power initiative provides free genetic testing, regardless of family health history, to screen for increased risk of cancer. Foundation funds will support expansion of Information is Power to underserved and underrepresented groups in Alabama’s Black Belt region. The project will bring the benefits of breast cancer prevention and early detection to underserved women in our communities.

Breast cancer metastasis to the brain is an uncurable outcome for patients. Many patients have underlying mutations that contribute to breast cancer. We will test how these common mutations may allow for metastasis to the brain using our state-of-the-art cell based modeling.