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Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer

Motahareh Mortazavi1, Fatemeh Moosavi1, Miriam Martini2

  • 1Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Critical Reviews in Oncology/Hematology
|June 21, 2022
PubMed

Insights

Pancreatic cancer (PDAC) often involves the PI3K/AKT/mTOR pathway. Targeting this pathway shows promise, but patient stratification is crucial for effective treatment strategies in clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) presents a poor prognosis.
  • The PI3K/AKT/mTOR pathway, a KRAS effector, regulates cancer hallmarks.

Purpose of the Study:

  • To analyze whole-genome data for PI3K/AKT/mTOR pathway aberrations in PDAC.
  • To evaluate preclinical and clinical evidence for PI3K/AKT/mTOR inhibitors in PDAC.
  • To examine combination therapies involving PI3K/AKT/mTOR inhibitors.

Main Methods:

  • Whole-genome analyses of PDAC patients.
  • Systematic review of preclinical studies on PI3K/AKT/mTOR targeting agents.
  • Critical evaluation of clinical trial data for PI3K/AKT/mTOR pathway inhibitors.
  • Assessment of combination therapies (chemotherapeutics, CDK, RTK, RAF/MEK/ERK inhibitors).

Main Results:

  • Frequent aberrant activation of PI3K/AKT/mTOR pathway components identified in PDAC.
  • Preclinical data strongly support the role of this pathway in PDAC.
  • Clinical trial results have been less promising than expected.
  • Combination therapies are being explored.

Conclusions:

  • Targeting the PI3K/AKT/mTOR pathway is a potential therapeutic strategy for PDAC.
  • Patient stratification based on biomarkers is essential for successful clinical application.
  • Biomarker-guided trials may unlock the therapeutic potential of PI3K/AKT/mTOR inhibitors in pancreatic cancer.
Keywords:
EverolimusGastrointestinal tumorsIdelalisibKinase inhibitorsPersonalized medicine

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