Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy

Appl Microbiol Biotechnol. 2020 Jan;104(2):575-587. doi: 10.1007/s00253-019-10257-8. Epub 2019 Dec 12.

Abstract

Autophagy is a highly conserved catabolic process and participates in a variety of cellular biological activities. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, as a critical regulator of autophagy, is involved in the initiation and promotion of a series of pathological disorders including various tumors. Autophagy also participates in regulating the balance between the tumor and the tumor microenvironment. Natural products have been considered a treasure of new drug discoveries and are of great value to medicine. Mounting evidence has suggested that numerous natural products are targeting PI3K/AKT/mTOR-mediated autophagy, thereby suppressing tumor growth. Furthermore, autophagy plays a "double-edged sword" role in different tumors. Targeting PI3K/AKT/mTOR-mediated autophagy is an important therapeutic strategy for a variety of tumors, and plays important roles in enhancing the chemosensitivity of tumor cells and avoiding drug resistance. Therefore, we summarized the roles of PI3K/AKT/mTOR-mediated autophagy in tumorigenesis, progression, and drug resistance of tumors, which may be utilized to design preferably therapeutic strategies for various tumors.

Keywords: Autophagy; Drug resistance; PI3K/AKT/mTOR; Tumor; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Carcinogenesis*
  • Humans
  • Neoplasms / physiopathology*
  • Neoplasms / therapy
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases