October 24, 2008
Ariad Reports Encouraging Preclinical Data From Prostate Cancer Study
Ariad Pharmaceuticals has reported encouraging preclinical data on the investigational mTOR inhibitor, deforolimus, alone or in combination with the anti-androgen agent, bicalutamide, in models of prostate cancer.
This investigational study shows that the combination inhibits the growth of prostate cancer cell lines in various model systems. This data provide the scientific rationale for an ongoing Phase II clinical trial examining the same combination in patients with advanced prostate cancer.Preclinical studies showed that the combination of deforolimus and bicalutamide had anti-tumor activity in an established prostate cancer model. Together, these agents were also found to inhibit the mTOR and androgen receptor signaling pathways in prostate cancer cells. Prostate specific antigen (PSA) levels are controlled by the androgen receptor pathway and may be used as an indicator of prostate tumor cell proliferation. In this study, PSA levels decreased following treatment with deforolimus and bicalutamide.
In this preclinical study, deforolimus alone was shown to inhibit proliferation of multiple prostate cancer cell lines. Deforolimus is a potent inhibitor of mTOR, a master switch that regulates cell growth and division.
Communication between mTOR and the androgen receptor pathway has been implicated in progression of prostate cancer from androgen-dependence to androgen-independence. Consistent with this hypothesis, the combination of deforolimus and bicalutamide blocked the growth of prostate cancer cells in both cell culture and mouse models, the company said.
In addition to this preclinical study, Ariad also presented data from its Phase I clinical trial evaluating the pharmacodynamic profile of oral deforolimus when administered in multiple dosing schedules. These data supported the dosing regimen being evaluated in the Phase III Succeed clinical trial of deforolimus in patients with metastatic soft-tissue and bone sarcomas.
Additionally, the company reported data on the molecular profiling of blood cells from a Phase Ib study of deforolimus in patients with advanced solid tumors.