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Ascenta Therapeutics Announces Positive Preliminary Results with AT-101 in Docetaxel Refractory Prostate Cancer
Date:2/27/2009

ffer recurrent, advanced disease after definitive local therapy with radiation or prostatectomy and systemic treatment. One process by which prostate cancers may develop resistance to systemic treatment is by increasing the expression of proteins that inhibit apoptosis (programmed cell death). The most recognized group of such proteins are the antiapoptotic members of the Bcl-2 family, including Bcl-2, Bcl-XL, and Mcl-1. Overexpression of Bcl-2 family proteins in human tumor specimens has been reported by several groups to be associated with recurrence, more advanced stage, treatment resistance, the development of hormone-resistance, and shortened survival in prostate cancer.

About AT-101

AT-101 is an orally-active, pan-Bcl-2 inhibitor (including Bcl-2, Bcl-xL, Bcl-w, and Mcl-1 inhibition), that has been shown to directly induce apoptosis by operating as a BH3 mimetic and indirectly as an independent upregulator of Noxa and Puma. By blocking the binding of Bcl-2 family members with proapoptotic proteins and upregulating specific proapoptotic factors, AT-101 lowers the threshold for cancer cells to undergo apoptosis in various tumor types. In Phase I and Phase II trials, AT-101 has demonstrated single-agent cytoreductive activity in chronic lymphocytic leukemia (CLL), non-Hodgkins lymphoma (NHL), and prostate cancer. Phase II combination trials are ongoing in hormone-refractory prostate cancer and non-small cell lung cancer (with Taxotere(R) [docetaxel]), B-cell malignancies (with Rituxan(R) [rituximab]), small cell lung cancer (with Hycamtin(R) [topotecan]), glioma (with Temodar(R) [temozolomide], +/- chemoradiotherapy [XRT]) and in esophageal cancer (with docetaxel, 5-fluorouracil and XRT). Recently, two double-blinded, randomized, controlled trials of the docetaxel + AT-101 combination were opened in hormone-refractory prostate cancer and non-small cell lung cancer, both indications in which docetaxel is approved as a single age
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