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Wistar receives $1.5 million Department of Defense grant to ready prostate drug for clinical use
Date:9/12/2013

nd are currently in the clinic, they have limited activity in cancer patients. This may reflect their inability to inhibit HSP90 in mitochondria, which are protected by their own membrane. Using combinatorial chemistry, Altieri and his colleagues created a molecule that would both target HSP90 and accumulate in mitochondria.

"Gamitrinib is, essentially, a two-piece molecule, one part drives it into mitochondria and the other inhibits HSP90," said Altieri. "This became a promising drug concept, one that might apply to multiple forms of advanced cancer, because only cancer cells seem to exploit mitochondrial HSP90 in relevant amounts."

Gamitrinib exploits a critical weakness of cancer cells. While mitochondria control energy production, they also control the inherent self-destruct mechanism within cells, a process called programmed cell death or apoptosis. It is a mechanism that is relevant to many forms of metastatic cancer, and Altieri believes that, in time, the drug will be used to treat many cancers in addition to prostate cancer. Over years of study, the Altieri laboratory has demonstrated how Gamitrinib can prime cancer cell mitochondria for destruction in cell cultures and animal models for many advanced forms of cancer.

The Department of Defense grant will enable the Altieri laboratory to make the final leap between laboratory science and trials in human subjects. The funds will allow Wistar to contract with third-party research organizations to conduct the formulation, toxicology, and pharmacology studies to demonstrate the drug's effectiveness and safety in anticipation of human trials. The funds will also support the development of a suitable biomarkera biological signature that could be measured in patients to demonstrate the effectiveness of Gamitrinib-based therapy.

"In our studies we have shown the mechanism by which Gamitrinib works and potential drug combinations that will kill metastatic prostate cancer cells mo
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Contact: Greg Lester
glester@wistar.org
215-898-3934
The Wistar Institute
Source:Eurekalert

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