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.
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.
|Basha, Riyaz; Connelly, Sarah F; Sankpal, Umesh T et al. (2016) Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution. J Nutr Biochem 31:77-87|
|Maji, Sayantan; Chaudhary, Pankaj; Akopova, Irina et al. (2016) Exosomal Annexin A2 Promotes Angiogenesis and Breast Cancer Metastasis. Mol Cancer Res :|
|Kokate, Rutika A; Chaudhary, Pankaj; Sun, Xiangle et al. (2016) Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy. Nanomedicine (Lond) 11:479-94|
|Kpetemey, Marilyne; Dasgupta, Subhamoy; Rajendiran, Smrithi et al. (2015) MIEN1, a novel interactor of Annexin A2, promotes tumor cell migration by enhancing AnxA2 cell surface expression. Mol Cancer 14:156|
|Rajendiran, Smrithi; Kpetemey, Marilyne; Maji, Sayantan et al. (2015) MIEN1 promotes oral cancer progression and implicates poor overall survival. Cancer Biol Ther 16:876-85|
|Kokate, Rutika A; Thamake, Sanjay I; Chaudhary, Pankaj et al. (2015) Enhancement of anti-tumor effect of particulate vaccine delivery system by 'bacteriomimetic' CpG functionalization of poly-lactic-co-glycolic acid nanoparticles. Nanomedicine (Lond) 10:915-29|
|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|
|Chaudhary, P; Thamake, S I; Shetty, P et al. (2014) Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies. Br J Cancer 111:2328-41|
|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|
|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|
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