Challenges and Emerging Opportunities for Targeting mTOR in Cancer

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...

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Published inCancer research (Chicago, Ill.) Vol. 82; no. 21; pp. 3884 - 3887
Main Authors Wood, Kris C, Gutkind, J Silvio
Format Journal Article
LanguageEnglish
Published United States 02.11.2022
Subjects
Humans
Neoplasms - pathology
Protein Kinase Inhibitors - pharmacology
Signal Transduction
Sirolimus
TOR Serine-Threonine Kinases - metabolism
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-22-0602