Targeted Therapy and Mechanisms of Drug Resistance in Breast Cancer

SIMPLE SUMMARY: Internationally, in women, breast cancer (BC) is the most common cancer type and is the leading cause of cancer-related death. There are two main histological classifications of BC, carcinoma in situ and carcinoma invasive. BC is further histologically subclassified as ductal carcinomas and lobular carcinomas. Once diagnosed, BC is typically treated based on the molecular subtype of cancer. The subtypes are based on the presence or absence of hormone receptors progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). The main molecular subtypes of BC include Luminal A (ER+, PR+, HER2-), Luminal B (ER+, PR+ HER2+), HER2 enriched (ER−, PR−, HER2+), and basal-like/ triple-negative BC (TNBC). People with hormone-positive (ER+ and or HER2+) BC are typically treated with endocrine therapy and chemotherapy, making them easier to treat. TNBC, on the other hand, is more challenging to treat due to the lack of hormone receptors and the aggressiveness of this form of cancer. Unfortunately, most therapies used to treat BC can often lead to drug resistance, relapse, and metastasis to other body parts. Due to its complexity and many mechanisms, it is difficult to overcome drug resistance. However, further research into potential drug targets and their relationship with drug resistance could help circumvent BC drug resistance. ABSTRACT: Breast cancer is the most common cause of cancer-related death in women worldwide. Multidrug resistance (MDR) has been a large hurdle in reducing BC death rates. The drug resistance mechanisms include increased drug efflux, enhanced DNA repair, senescence escape, epigenetic alterations, tumor heterogeneity, tumor microenvironment (TME), and the epithelial-to-mesenchymal transition (EMT), which make it challenging to overcome. This review aims to explain the mechanisms of resistance in BC further, identify viable drug targets, and elucidate how those targets relate to the progression of BC and drug resistance.