Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer

Valerie Nelson, Jessica K. Altman, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Introduction: Because of the central role of the mammalian target of rapamycin (mTOR) pathway in the control and distribution of signals essential for mRNA translation of mitogenic genes and generation of oncogenic proteins, effective targeting of mTOR remains a major goal in medical oncology. Areas covered: This article summarizes preclinical and clinical studies relating to the next generation of mTOR inhibitors. While rapalogs have shown activity in the treatment of breast, renal and neuroendocrine tumors, these agents do not block mTORC2, one of the two major protein complexes in which mTOR participates. In addition, there is emerging evidence that these agents only partially block mTORC1, underscoring the need for more effective mTOR inhibitors. In recent years, catalytic mTOR inhibitors have been developed, which block both mTORC1 and mTORC2. Such inhibitors show generally better activity in preclinical models than rapalogs and some of them have been or are in clinical trials in humans. Expert opinion: It is anticipated that with the continuous expansion of work in this research field, the therapeutic potential of targeting the mTOR pathway for the treatment of several malignancies will reach a maximum point in the next few years and may ultimately change the way we treat several malignant tumors.

Original languageEnglish (US)
Pages (from-to)715-722
Number of pages8
JournalExpert Opinion on Investigational Drugs
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Cancer
  • Leukemia
  • MRNA translation
  • MTORC1
  • MTORC2
  • Mammalian target of rapamycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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