Autophagy therapeutics: preclinical basis and initial clinical studies

Cancer Chemother Pharmacol. 2018 Dec;82(6):923-934. doi: 10.1007/s00280-018-3688-3. Epub 2018 Sep 17.

Abstract

Autophagy captures and degrades intracellular components such as proteins and organelles to sustain metabolism and homeostasis. Rapidly accumulating attention is being paid to the role of autophagy in the development of cancer, which makes autophagy attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that autophagy dysregulation is causal in many cases of cancer, with autophagy acting as tumor suppressors or tumor promoters, and autophagy inhibitor or promoter has shown promise in preclinical studies. The autophagy-targeted therapeutics using chloroquine/hydroxychloroquine have reached clinical development for treating cancer, but these drugs are actually not efficient probably because of a reduced penetration within the tumor. In this review, we first discuss the discoveries related to dual function of autophagy in cancer. Then, we provide an overview of preclinical studies and clinical trials involved in the development of autophagy therapeutics and finally discuss the future of such therapies.

Keywords: Autophagy; Cancer; Clinical trials; Functional studies; Preclinical studies; Therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Cell Survival / drug effects
  • Chloroquine / administration & dosage
  • Chloroquine / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Hydroxychloroquine / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Hydroxychloroquine
  • Chloroquine