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mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why? / 医学前沿
Frontiers of Medicine ; (4): 221-231, 2021.
Article in English | WPRIM | ID: wpr-880964
ABSTRACT
The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphatidylinositol 3-Kinases / Glycogen Synthase Kinase 3 / Protein Kinase Inhibitors / Proto-Oncogene Proteins c-akt / TOR Serine-Threonine Kinases / Mechanistic Target of Rapamycin Complex 2 / Neoplasms Language: English Journal: Frontiers of Medicine Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Phosphatidylinositol 3-Kinases / Glycogen Synthase Kinase 3 / Protein Kinase Inhibitors / Proto-Oncogene Proteins c-akt / TOR Serine-Threonine Kinases / Mechanistic Target of Rapamycin Complex 2 / Neoplasms Language: English Journal: Frontiers of Medicine Year: 2021 Type: Article