African-American women are disproportionately affected by triple negative breast cancer (TNBC), a form of breast cancer that does not express the three widely used biomarkers and therapeutic targets, namely Her-2, estrogen receptor and progesterone receptor. Consequently, these women do not benefit from the novel therapies (eg., Herceptin therapy) targeting the three biomarkers. TNBC are very aggressive, resulting in higher mortality rate in African-American women than women in other population. While TNBC is initially sensitive to chemotherapy, these women develop chemoresistance with no alternative treatment regimen available. Thus, there is a critical need to identify novel biomarkers for TNBC and develop specific therapeutic strategies to combat this health disparity. In preliminary studies, we have identified annexin A2 as a putative biomarker for TNBC. When Her-2 is negative, we find annexin A2 expression to be significantly increased, and conversely when Her-2 is overexpressed, annexin A2 expression is decreased. We hypothesize that AnxA2 overexpression accounts for the disproportionate occurrence of TNBC in African American women, and that AnxA2 is a useful biomarker and therapeutic target for TNBC. We will test this hypothesis through the following specific aims: 1) To integrate TNBC as a focus of education in an ongoing primary prevention program targeting high nsk AA women, 2) To establish the correlation of AnxA2 expression with poor pathological, prognostic variables and ethnicity in TNBC patients, and validate AnxA2 as a diagnostic biomarker for TNBC patients. 3) To delineate AnxA2-EGFR mediated downstream signaling pathway which regulates cancer cell proliferation, migration and invasion in TNBC, and 4) To establish AnxA2 as a therapeutic target in triple negative breast cancer. Our expectation is that successful completion of the proposed work will identify a specific biomarker for TNBC that could be targeted by novel therapeutic strategies. The proposed investigations will help in understanding the role of AnxA2 expression in the incidence of TNBC in various ethnic groups.

Public Health Relevance

Triple negative breast cancer, disproportionately affect Afncan-American women and is a significant health disparity problem. Our research is aimed at identifying novel biomarkers and devising therapeutic strategies to solve this public health problem.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
Exploratory Grants (P20)
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Special Emphasis Panel (ZMD1-RN)
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University of North Texas
Fort Worth
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Griner, Nicholas B; Young, Denise; Chaudhary, Pankaj et al. (2015) ERG oncoprotein inhibits ANXA2 expression and function in prostate cancer. Mol Cancer Res 13:368-79
Rajendiran, Smrithi; Parwani, Anil V; Hare, Richard J et al. (2014) MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1. Mol Cancer 13:250
Valapala, Mallika; Maji, Sayantan; Borejdo, Julian et al. (2014) Cell surface translocation of annexin A2 facilitates glutamate-induced extracellular proteolysis. J Biol Chem 289:15915-26
Chaudhary, Pankaj; Vishwanatha, Jamboor K (2014) c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Biochem Pharmacol 91:457-73
Chaudhary, Pankaj; Sharma, Rajendra; Sahu, Mukesh et al. (2013) 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway. J Biol Chem 288:20532-46