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

Motahareh Mortazavi, Fatemeh Moosavi, Miriam Martini, Elisa Giovannetti, Omidreza Firuzi

Research output: Contribution to journalReview articleAcademicpeer-review

26 Citations (Scopus)


Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses among all malignancies. PI3K/AKT/mTOR signaling pathway, a main downstream effector of KRAS is involved in the regulation of key hallmarks of cancer. We here report that whole-genome analyses demonstrate the frequent involvement of aberrant activations of PI3K/AKT/mTOR pathway components in PDAC patients and critically evaluate preclinical and clinical evidence on the application of PI3K/AKT/mTOR pathway targeting agents. Combinations of these agents with chemotherapeutics or other targeted therapies, including the modulators of cyclin-dependent kinases, receptor tyrosine kinases and RAF/MEK/ERK pathway are also examined. Although human genetic studies and preclinical pharmacological investigations have provided strong evidence on the role of PI3K/AKT/mTOR pathway in PDAC, clinical studies in general have not been as promising. Patient stratification seems to be the key missing point and with the advent of biomarker-guided clinical trials, targeting PI3K/AKT/mTOR pathway could provide valuable assets for treatment of pancreatic cancer patients.
Original languageEnglish
Article number103749
JournalCritical Reviews in Oncology/Hematology
Publication statusPublished - 1 Aug 2022


  • Everolimus
  • Gastrointestinal tumors
  • Idelalisib
  • Kinase inhibitors
  • Personalized medicine

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