Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma

Int J Oncol. 2019 Dec;55(6):1213-1222. doi: 10.3892/ijo.2019.4902. Epub 2019 Oct 18.

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children and adolescents. Currently, surgical resection combined with adjuvant chemotherapy has been standardized for OS treatment. Despite great advances in chemotherapy for OS, its clinical prognosis remains far from satisfactory; this is due to chemoresistance, which has become a major obstacle to improving OS treatment. Autophagy, a catabolic process through which cells eliminate and recycle their own damaged proteins and organelles to provide energy, can be activated by chemotherapeutic drugs. Accumulating evidence has indicated that autophagy plays the dual role in the regulation of OS chemoresistance by either promoting drug resistance or increasing drug sensitivity. The aim of the present review was to demonstrate thatautophagy has both a cytoprotective and an autophagic cell death function in OS chemoresistance. In addition, methods to detect autophagy, autophagy inducers and inhibitors, as well as autophagy‑mediated metastasis, immunotherapy and clinical prognosis are also discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Autophagic Cell Death / drug effects*
  • Autophagic Cell Death / immunology
  • Autophagy / drug effects*
  • Autophagy / immunology
  • Bone Neoplasms / immunology
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy*
  • Bone and Bones / pathology
  • Bone and Bones / surgery
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemotherapy, Adjuvant / methods
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / immunology
  • Humans
  • Mice
  • Osteosarcoma / immunology
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • Prognosis
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Survival Rate
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Immunological