Targeted therapy in sarcomas: mammalian target of rapamycin inhibitors from bench to bedside.
BACKGROUND
Sarcomas are rare heterogeneous malignancies of mesenchymal origin relatively common during childhood. Disruption of the mammalian target of rapamycin (mTOR) pathway is a very common event during the tumorigenesis of several types of cancer. In particular, strong preclinical evidences suggest pivotal roles of this pathway during the sarcomagenesis. Therefore, the inhibition of mTOR via rapamycin, rapamycin analogs (rapalogs) and ATP-competitive inhibitors seems to be a promising path to follow for a fully tailored therapy.


METHODS
The aim of the present review is to summarize the available data about the mechanisms of mTOR pathway, its biological implications and its possible role in the pathogenesis of soft tissue sarcoma. Moreover, preclinical and clinical evidences of different mTOR inhibitors in the treatment of sarcomas are reported.


CONCLUSIONS
Early studies with mTOR inhibitors have demonstrated promising antitumor activity in patients with metastatic sarcoma who have failed standard treatments: that is why mTOR inhibitors represents today a promising chance to improve the prognosis of those patients affected by these rare disease, which is today still extremely poor.
University Campus Bio-Medico, Medical Oncology, via Alvaro del Portillo, 200, Rome, Italy.
Bruno
B
Vincenzi
Andrea
A
Napolitano
Loretta
L
D'Onofrio
Anna Maria
AM
Frezza
Marianna
M
Silletta
Olga
O
Venditti
Daniele
D
Santini
Giuseppe
G
Tonini
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D057170:Translational Research, Biomedical
D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus