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mTOR as a therapeutic target in patients with gastric cancer

Salah-Eddin Al-Batran1, Michel Ducreux, Atsushi Ohtsu

  • 1Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt, Germany. albatran@aol.com

International Journal of Cancer
|September 8, 2011
PubMed

Insights

Targeting the mammalian target of rapamycin (mTOR) pathway shows promise for advanced gastric cancer. mTOR inhibitors like everolimus are being studied for improved survival in patients with this disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Advanced gastric cancer has poor long-term outcomes with current chemotherapy.
  • Mammalian target of rapamycin (mTOR) pathway activation is observed in gastric cancer.
  • Novel targeted agents are needed for improved survival benefits.

Purpose of the Study:

  • To review the relevance of the mTOR pathway in gastric cancer pathogenesis.
  • To explore the potential of mTOR as a therapeutic target in gastric cancer.
  • To present clinical data on mTOR inhibitors for gastric cancer.

Main Methods:

  • Review of preclinical data on mTOR pathway suppression in gastric cancer models.
  • Analysis of clinical data from Phase I/II studies of mTOR inhibitors.
  • Examination of ongoing Phase II/III clinical trials.

Main Results:

  • Preclinical data indicate mTOR pathway suppression inhibits gastric cancer cell proliferation and delays tumor progression.
  • The mTOR inhibitor everolimus demonstrated activity and tolerability in Phase I/II studies for refractory metastatic gastric cancer.
  • Everolimus is currently under investigation in Phase II/III trials.

Conclusions:

  • The mTOR pathway is a relevant therapeutic target for gastric cancer.
  • Everolimus shows promise as a treatment for advanced gastric cancer, alone or with chemotherapy.
  • Targeted inhibition of mTOR may offer a survival benefit for gastric cancer patients.

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