期刊
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
卷 176, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2022.103749
关键词
Personalized medicine; Kinase inhibitors; Gastrointestinal tumors; Everolimus; Idelalisib
资金
- Shiraz University of Medical Sciences [25318]
This study highlights the role of PI3K/AKT/mTOR pathway in pancreatic ductal adenocarcinoma, but clinical studies have not been promising. Patient stratification is identified as a crucial factor.
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 activa-tions 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.
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