title: Pharmacological inhibitors of autophagy as novel cancer therapeutic agents.
abstract: Autophagy is an evolutionarily conserved cellular degradative process in which intracellular components (cellular proteins and organelles) are engulfed in autophagosomes which then fuse with lysosomes to form autolysosome for degradation. Autophagy is closely implicated in various physio-pathological processes and human diseases. Among them, the roles of autophagy in cancer have been extensively studied. Increasing evidence has demonstrated that inhibiting autophagy is a novel and promising approach in cancer therapy, based on the notion that autophagy is a pro-survival mechanism in cancer cells under therapeutic stress, and induction of autophagy is associated with chemoresistance of cancer cells to chemotherapeutic agents. Thus, suppression of autophagy would sensitize resistance tumor cells to cancer therapeutic agents, thereby supporting the clinical application of autophagy inhibitors. In recent years, significant progress has been achieved in developing autophagy inhibitors and testing their therapeutical potential, either as standalone or as adjuvant therapeutic agents, in cell and animal models, and more importantly in clinical trials. In this review, we will discuss some of these recent advances in development of novel small molecules autophagy inhibitors and their mechanisms of action, together with their applications in clinical trials.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
authors.forename: Qidong
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore. Electronic address: phsshm@nus.edu.sg.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries