An overview of the mTOR pathway as a target in cancer therapy

Ryan D. Gentzler, Jessica K Altman, Leonidas C Platanias*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Introduction: The mammalian target of rapamycin (mTOR) signaling cascade is a key regulatory pathway controlling initiation of mRNA translation in mammalian cells. The mTOR inhibitor rapamycin and its derivatives have shown potent antineoplastic activities in many preclinical models and clinical trials. First-generation mTOR inhibitors are now FDA-approved for the treatment of renal cell carcinoma. Areas covered: This article reviews the components of the mTOR pathway and their normal functions, highlighting the most common alterations in the pathway, seen in various human malignancies. It also discusses elements and effectors of this signaling cascade and reviews the therapeutic relevance of pharmacological inhibitors of the pathway in several malignancies, including lymphomas, leukemias, sarcomas, renal cell carcinoma, and breast cancer. Expert opinion: mTOR targeting is a highly promising therapeutic approach. First-generation mTOR inhibitors have already shown substantial activity in the treatment of certain tumors, while the emergence of second-generation catalytic mTOR inhibitors provides a better approach to target the pathway in malignant cells and has raised the potential for better clinical outcomes in the future.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalExpert Opinion on Therapeutic Targets
Volume16
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • AKT
  • Breast cancer
  • Everolimus
  • Leukemia
  • Lymphoma
  • MTOR
  • PI3K
  • PTEN
  • Rapamycin
  • Renal cell carcinoma
  • Ridaforolimus
  • Sarcoma
  • Sirolimus
  • Temsirolimus
  • TORC1
  • TORC2

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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