Targeted Drug Therapy to Overcome Chemoresistance in Triple-negative Breast Cancer

Triple-negative Breast Cancer (TNBC) is the most aggressive and prevailing breast cancer subtype. The chemotherapeutics used in the treatment of TNBC stiffer from chemoresistance, dose-limiting toxicitics and off-target side effects. As a result, conventional chemotherapeutics are unable to prevent tumor growth, metastasis and result in failure of therapy. Various new targets such as BCSCs surface markers (CD44, CD133, ALDH1), signaling pathways (IL-6/JAK/STAT3, notch), pro and anti-apoptotic proteins (Bcl-2, Bcl-xL, DR4, DR5), hypoxic factors (HIF-1 alpha, HIF-2 alpha) and drug efflux transporters (ABCC1, ABCG2 and ABCB1) have been exploited to treat TNBC. Further, to improve the efficacy and safety of conventional chemotherapeutics, researchers have tried to deliver anticancer agents specifically to the TNBCs using nanocarrier based drug delivery. In this re- view, an effort has been made to highlight the various factors responsible for the chemoresistance in TNBC, novel molecular targets of TNBC and nano-delivery systems employed to achieve site-specific drug delivery to improve efficacy and reduce off-target side effects.