Ariad Pharmaceuticals Inc fka ARIA

[DonShimoda]

Updating progress in sarcoma therapy with mTOR inhibitors - June 29, 2010 Annals of Oncology

http://annonc.oxfordjournals.org/content/early/2010/06/29/annonc.mdq307.full

"Sarcoma presents a different therapeutic challenge compared with other solid tumours both because of the limited success of traditional treatment approaches and because monitoring the response of sarcoma lesions to therapy is not straightforward. The PI3K–Akt–mTOR pathway is an exciting target for therapy in many types of solid malignancy and its blockade represents an opportunity to improve outcomes in poor prognosis sarcoma. Activation of the PI3K–Akt–mTOR pathway is implicated both in the establishment of tumours and as an alternative signalling pathway in the development of resistance to antineoplastic therapy via PI3k–Akt or PTEN. Promising results have been observed with mTOR inhibitors both as monotherapy and in combination with cytotoxic and targeted therapies, where mTOR blockade has been shown to circumvent the development of resistance.

The varying degrees of therapeutic success in different tumour types with the available synthetic rapamycin analogues indicate that they are not therapeutically equivalent (emphasis added), and consequently, more research is necessary to define where each agent fits into the treatment strategy for different cancers. Currently, encouraging prolongation of survival in soft tissue sarcoma has been observed with ridaforolimus, and phase III data are eagerly anticipated for this drug."