Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Med Res Rev. 2020 May;40(3):1002-1060. doi: 10.1002/med.21646. Epub 2019 Nov 19.

Abstract

Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.

Keywords: autophagy; autophagy modulators; biomarkers; esophageal squamous cell carcinoma; exosomes; oral squamous cell carcinoma; targeted therapy.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Alcohol Drinking
  • Antineoplastic Agents / pharmacology
  • Autophagosomes / metabolism
  • Autophagy / drug effects*
  • Autophagy / radiation effects*
  • Biomarkers / metabolism
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / radiotherapy
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / radiotherapy
  • Genetic Predisposition to Disease
  • Humans
  • Lysosomes / metabolism
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / radiotherapy
  • Prognosis
  • Radiotherapy / methods
  • Signal Transduction
  • Tobacco Products
  • Virus Diseases / complications

Substances

  • Antineoplastic Agents
  • Biomarkers
  • AMP-Activated Protein Kinases