Preclinical Studies Show Potential Progress Toward Identifying Specific Tumor Types With Higher Likelihood of Demonstrating Response to Anti-Cancer Compounds Early in Clinical D... (athione transferases GSTP1-1 and GSTM2-2...)

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Preclinical Studies Show Potential Progress Toward Identifying Specific Tumor Types With Higher Likelihood of Demonstrating Response to Anti-Cancer Compounds Early in Clinical Development

Date:10/25/2007

athione transferases GSTP1-1 and GSTM2-2 (Abstract #C249)

Data were also presented on the mechanism of action of brostallicin and its interaction with glutathione transferases. "It is well established that both glutathione and glutathione S-transferase are overexpressed in many types of cancer cells in comparison to normal tissues and are also involved in the mechanism of resistance to several antitumor drugs," noted Robert B. MacArthur, Pharm.D., Vice President of Clinical and Regulatory Affairs for Systems Medicine. "It is also known that brostallicin's activity is enhanced in the presence of both glutathione and glutathione S-transferase and that tumor cells expressing relatively high levels of glutathione and glutathione S-transferase are more susceptible to brostallicin's antitumor activity."

These data establish for the first time that brostallicin interacts with each enzyme in a different manner. "Several human tumors display increased levels of Pi and Mu class of glutathione S-transferase and these data support the value of targeting those tumors in the development of brostallicin," MacArthur concluded.

About Brostallicin

Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumor models. Brostallicin binds covalently to DNA within the DNA minor groove interfering with DNA division and leading to tumor cell death. More than 200 patients have been treated with brostallicin in single-agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumor types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma met its pre-defined activity and safety hurdles and resulted in a first-line phase II study that is currently being conduct
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SOURCE Cell Therapeutics, Inc.
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