mTOR as a therapeutic target in patients with gastric cancer

The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived...

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Bibliographic Details
Published in:International journal of cancer 2012-02, Vol.130 (3), p.491-496
Main Authors: Al-Batran, Salah-Eddin, Ducreux, Michel, Ohtsu, Atsushi
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Cancer
Chemotherapy
Everolimus
gastric adenocarcinoma
Gastric cancer
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Medical research
Medical sciences
Molecular Targeted Therapy
mTOR
mTOR inhibitors
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Signal Transduction - drug effects
Sirolimus - analogs & derivatives
Sirolimus - pharmacology
Sirolimus - therapeutic use
Stomach Neoplasms - drug therapy
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
TOR Serine-Threonine Kinases - antagonists & inhibitors
Tumors
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Summary:The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy‐refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.26396