Breast cancers with germline mutations in the BRCA1 and triple negative breast cancers (TNBC) are known to respond to drugs that target DNA repair pathways. Earlier study from our group has shown that chemo preventive agents that target base-excision DNA repair activity potentially enhance the DNA repair abilities of mutant BRCA1 and TNBC tumors, thereby, reducing tumor onset and delaying metastasis. More recently, we have developed novel small molecules and investigated their potential to protect BRCA1 mutant and TNBC cells from oxidative DNA damage by enhancing the DNA repair function. Our study shows that these small molecules are well tolerated and have negligible toxicity. Furthermore, we found that the ‘hit’ compound protects breast cancer cells from hydrogen peroxide mediated oxidative DNA damage. Modified analogs of the ‘hit’ enhance DNA repair in TNBC cells. Thus, this study offers a new approach to chemoprevention by enhancing DNA repair and protecting cells from oxidative DNA damage.

Small molecules facilitating DNA repair in breast cancer cells

256th National Meeting (2018)

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