Autophagy therapeutics: preclinical basis and initial clinical studies

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.

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