Abstract A093: Addressing disparities in breast cancer: Using DNA damage response to bridge the gap
Authors: Smith Shanna J , Li Caroline M , Malkas Linda H 
Published: September 2020

Breast cancer currently ranks as the most common and the second most fatal form of cancer affecting women living in the United States. Due to increased awareness, along with advancements in screening techniques and improvement in treatment options, breast cancer has become a more manageable disease. While breast cancer-related deaths have, on average, continued to decrease, gaping health disparities along racial lines have become more prominent. For example African American women living in the greater Los Angeles area have a 70% greater risk of dying from breast cancer, as compared non-Hispanic Caucasian women. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer that disproportionately affects African American women. TN tumors lack the overexpression of estrogen receptor (ER), progesterone receptor (PR), and human estrogen receptor 2 (HER2). This high-grade ductal carcinoma is a more aggressive phenotype that carries with it a greater risk of relapse versus other breast cancer subtypes. Currently, there is a lack of effective treatment options for TNBC, as molecular targets specific to TNBC have yet to be identified and conventional therapies are highly toxic in nature with a high risk of failure. There is a clear need to develop targeted, less cytotoxic therapeutic agents for patients suffering from TNBC. The most common chemotherapeutic or radiotherapeutic agents function by damaging DNA or interfering with DNA replication, and advances in recent years have contributed to a better understanding of the roles key proteins play in DNA damage response pathways. The effectiveness of conventional therapies could be enhanced if specific targets within the DNA damage response pathways were altered or blocked. By selectively sensitizing cancer cells relative to normal tissues, these novel targets have the potential to drastically improve the therapeutic capability. Our lab has previously developed a compound (AOH 1996) that displays the ability to disrupt DNA repair pathways relying on interactions with proliferating cell nuclear antigen (PCNA). Interestingly, AOH 1996 appears to be more potent in a representative African American TNBC cell line (MDA-MB-468) versus a Caucasian counterpart (MDA-MB-231). The data indicates the repair mechanism in the MDA-MB-468 cell line is more dependent on PCNA-controlled DNA repair pathways. This suggests there is a therapeutic target in TNBC specific to African Americans that can exploited to develop more effective treatments in this particularly disadvantaged population.

Citation Format: Shanna J Smith, Caroline M Li, Linda H Malkas. Addressing disparities in breast cancer: Using DNA damage response to bridge the gap [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A093.