Tailoring mTOR-based therapy: Molecular evidence and clinical challenges

Gaetano Santulli, Hana Totary-Jain

Research output: Contribution to journalReview article

53 Scopus citations

Abstract

The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism. The mTOR pathway is dysregulated in a number of human pathologies including cancer, diabetes, obesity, autoimmune disorders, neurological disease and aging. Ongoing clinical trials testing mTOR-targeted treatments number in the hundreds and underscore its therapeutic potential. To date mTOR inhibitors are clinically approved to prevent organ rejection, to inhibit restenosis after angioplasty, and to treat several advanced cancers. In this review we discuss the continuously evolving field of mTOR pharmacogenomics, as well as highlight the emerging efforts in identifying diagnostic and prognostic markers, including miRNAs, in order to assess successful therapeutic responses.

Original languageEnglish (US)
Pages (from-to)1517-1526
Number of pages10
JournalPharmacogenomics
Volume14
Issue number12
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Keywords

  • FKBP12
  • biomarkers
  • cancer
  • cardiovascular disease
  • clinical trials
  • dual inhibitors
  • mTOR
  • microRNA
  • rapamycin
  • resistance

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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