Challenges and Emerging Opportunities for Targeting mTOR in Cancer
Kris C. Wood, J. Silvio Gutkind
Abstract
The mechanistic target of rapamycin (mTOR) plays a key role in normal and malignant cell growth. However, pharmacologic targeting of mTOR in cancer has shown little clinical benefit, in spite of aberrant hyperactivation of mTOR in most solid tumors. Here, we discuss possible reasons for the reduced clinical efficacy of mTOR inhibition and highlight lessons learned from recent combination clinical trials and approved indications of mTOR inhibitors in cancer. We also discuss how the emerging systems level understanding of mTOR signaling in cancer can be exploited for the clinical development of novel multimodal precision targeted therapies and immunotherapies aimed at achieving tumor remission.
Topics & Concepts
PI3K/AKT/mTOR pathwayDiscovery and development of mTOR inhibitorsClinical trialCancerMedicineCancer researchRPTORMechanistic target of rapamycinmTORC2BioinformaticsBiologySignal transductionInternal medicinemTORC1BiochemistryPI3K/AKT/mTOR signaling in cancerPolyamine Metabolism and ApplicationsMast cells and histamine