Mammalian target of rapamycin inhibitors in sarcomas.
OBJECTIVE
Sarcomas are a rare malignancy accounting for less than 1% of all cancers diagnosed annually. Standard chemotherapy has a response rate of around 25% and newer agents are needed to improve the outcome in patients with advanced sarcomas. The mammalian target of rapamycin plays a central role in cell growth, proliferation, and apoptosis and its inhibition has demonstrated antitumor activity in many tumors and shows promise against sarcomas.


RESULTS
Recent studies of mammalian target of rapamycin inhibitors in sarcomas have demonstrated clinical benefit response in sarcomas.


CONCLUSIONS
Clinical benefit response uses standard Response Evaluation Criteria in Solid Tumors of complete response and partial response as well as stable disease lasting at least 4 months as an endpoint. This endpoint has been shown to select promising new agents against sarcomas. Using this endpoint, the use of the mammalian target of rapamycin inhibitor AP23573 has demonstrated activity against sarcomas. The use of the inhibitor RAD001 (everolimus) along with imatinib in patients with imatinib resistant gastrointestinal stromal tumor has shown promise. Future studies will need to be performed to determine the clinical differences among the mammalian target of rapamycin inhibitors in different subsets of sarcomas.
Okuno
Scott
S
Medical Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. okuno.scott@mayo.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D006801:Humans; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus