Molecular mechanisms underlying autophagy-mediated treatment resistance in cancer

Abstract

Despite advances in diagnostic tools and therapeutic options, treatment resistance remains a challenge for many cancer patients. Recent studies have found evidence that autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation and recycling, contributes to treatment resistance in different cancer types. A role for autophagy in resistance to chemotherapies and targeted therapies has been described based largely on associations with various signaling pathways, including MAPK and PI3K/AKT signaling. However, our current understanding of the molecular mechanisms underlying the role of autophagy in facilitating treatment resistance remains limited. Here we provide a comprehensive summary of the evidence linking autophagy to major signaling pathways in the context of treatment resistance and tumor progression, and then highlight recently emerged molecular mechanisms underlying autophagy and the p62/KEAP1/NRF2 and FOXO3A/PUMA axes in chemoresistance.