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Mechanisms of resistance to mTOR inhibitors

Luigi Formisano1, Fabiana Napolitano1, Roberta Rosa1

  • 1Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131, Naples, Italy.

Critical Reviews in Oncology/Hematology
|February 5, 2020
PubMed

Insights

Resistance to PI3K/AKT/mTOR pathway inhibitors is common due to the key role of mTOR in cell survival. This review explores resistance mechanisms to mTOR inhibitors in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The PI3K/AKT/mTOR pathway is frequently disrupted in various tumors, driving uncontrolled cell proliferation and growth.
  • Inhibitors targeting the mammalian target of rapamycin (mTOR) have been developed, but resistance mechanisms emerge rapidly.
  • Despite resistance, mTOR inhibitors show clinical promise in specific cancers like breast cancer and renal cell carcinoma.

Purpose of the Study:

  • To review and describe the mechanisms of resistance to mTOR inhibitors.
  • To explore both preclinical and clinical perspectives on resistance development.
  • To inform the selection of patient populations likely to respond to mTOR inhibitors.

Main Methods:

  • Literature review of preclinical studies on mTOR inhibitor resistance.
  • Analysis of clinical trial data and patient outcomes related to mTOR inhibitors.
  • Synthesis of information on predictive factors for treatment response.

Main Results:

  • Identified key roles of mTOR in cell survival leading to rapid resistance.
  • Documented clinical efficacy of mTOR inhibitors in specific tumor types.
  • Highlighted the need for predictive biomarkers to guide treatment decisions.

Conclusions:

  • Understanding resistance mechanisms is crucial for optimizing mTOR inhibitor therapy.
  • Further research into predictive factors can improve patient selection and treatment outcomes.
  • mTOR inhibitors remain a valuable therapeutic option when resistance is addressed.
Keywords:
Mechanisms of resistancePredictive factorsmTOR inhibitors

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