Autophagy and apoptotic crosstalk: Mechanism of therapeutic resistance in HER2-positive breast cancer

Abstract

While breast cancer patients benefit from the use of HER2 inhibitors, many fail therapy and become resistant to treatment, indicating a critical need to prevent treatment failure. A number of studies have emerged that highlight the catabolic process of autophagy in breast cancer as a mechanism of resistance to chemotherapy and targeted inhibitors. Furthermore, recent research has begun to dissect how autophagy signaling crosstalks with apoptotic signaling. Thus, a possible strategy in fighting resistance is to couple targeting of apoptotic and autophagy signaling pathways. In this review, we discuss how cellular response by autophagy circumvents cell death to promote resistance of breast cancers to HER2 inhibitors, as well as the potential avenues of therapeutic intervention.