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Targeting mTOR pathways in human malignancies

Angelica Fasolo1, Cristiana Sessa

  • 1Unit of New Drugs & Innovative Therapies, Department of Medical Oncology Fondazione Centro San Raffaele del Monte Tabor, Via Olgettina n° 60, 20132, Milano, Italy. fasolo.angelica@hsr.it

Current Pharmaceutical Design
|April 6, 2012
PubMed
Abstract

Insights

The mammalian target of rapamycin (mTOR) pathway is crucial in cancer. First-generation mTOR inhibitors like temsirolimus and everolimus show efficacy, while newer inhibitors demonstrate promising preclinical anti-cancer activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth, survival, and angiogenesis.
  • Dysregulation of the PI3K/AKT/mTOR pathway is common in human cancers, making it a significant therapeutic target.

Purpose of the Study:

  • To review current data on the mTOR pathway and its inhibitors in cancer treatment.
  • To summarize preclinical and clinical findings for first-generation mTOR inhibitors (temsirolimus, everolimus, deferolimus).
  • To discuss the rationale and data for second-generation mTOR inhibitors.

Main Methods:

  • Comprehensive literature review of published studies on the mTOR pathway.
  • Analysis of data on rapalogs and novel mTOR inhibitors in cancer research.

Main Results:

  • Temsirolimus and everolimus are approved for metastatic renal cell carcinoma (RCC) and other cancers.
  • Newer mTOR inhibitors exhibit potent in vitro and in vivo antiproliferative activity.
  • Preclinical studies show favorable safety profiles and tumor regression with novel mTOR inhibitors.

Conclusions:

  • First-generation mTOR inhibitors have established roles in treating specific cancers.
  • Second-generation mTOR inhibitors show significant promise as single agents or in combination therapies.
  • Further clinical evaluation of novel mTOR inhibitors is warranted for broad anti-cancer applications.

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