MTOR cross-talk in cancer and potential for combination therapy

Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella

Research output: Contribution to journalReview article

Abstract

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer. Single-agent mTOR targeting, mostly using rapalogs, has so far met limited clinical success; however, due to the extensive cross-talk between mTOR and other pathways, combined approaches are the most promising avenues to improve clinical efficacy of available therapeutics and overcome drug resistance. This review provides a brief and up-to-date narrative on the regulation of mTOR function, the relative contributions of mTORC1 and mTORC2 complexes to cancer development and progression, and prospects for mTOR inhibition as a therapeutic strategy.

Original languageEnglish
Article number23
JournalCancers
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 19 2018

Keywords

  • Cancer
  • Cross-talk
  • MTORC1
  • MTORC2
  • Targeted therapies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Conciatori, F., Ciuffreda, L., Bazzichetto, C., Falcone, I., Pilotto, S., Bria, E., Cognetti, F., & Milella, M. (2018). MTOR cross-talk in cancer and potential for combination therapy. Cancers, 10(1), [23]. https://doi.org/10.3390/cancers10010023