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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

y and toxicity and gain further insight into the molecular mechanism by which these new Src inhibitors retain potent activity against all tested imatinib resistant BCR-ABL mutants, including the BCR-ABL T315I mutant, which is generally refractory to other Src and Aurora Kinase inhibitors," said Mousses.

Antitumor activity of brostallicin on human prostatic cancer: role of combination with hypomethylating agents (Abstract #A288)

Data were presented that show brostallicin, when combined with hypomethylating agents such as zebularine, may convert resistant tumors into tumors sensitive to brostallicin. The data suggest that interaction between zebularine and brostallicin could be beneficial to patients with prostate cancer and that the use of other hypomethylating agents in combination with brostallicin should be explored. The study results support a potential clinical trial of zebularine in combination with brostallicin.

Brostallicin induces DNA damage measured by histone H2AX phosphorylation independently of the nucleotide excision repair pathways. (Abstract #B77)

Yves Pommier, M.D., Ph.D., Chief of the Laboratory of Molecular Pharmacology at the Center for Cancer Research at the NCI evaluated various cell lines known to be differentially sensitive to ecteinascidin 743 (a minor groove binder). Data showed that brostallicin retained potent cytotoxicity in the submicromolar range in cell lines previously identified to be resistant to ecteinascidin 743. In addition, the study showed brostallicin is less dependent on the nucleotide excision repair (NER) gene than ecteinascidin 743 and that cells selected for resistance to ecteinascidin 743 showed no cross resistance to brostallicin. The study also suggested gamma-H2AX, a major regulator of cellular responses to DNA damage, could be considered a pharmacodynamic biomarker for the clinical development of brostallicin.

Occurrence and mode of the interaction between brostallicin and the human glut
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SOURCE Cell Therapeutics, Inc.
Copyright©2007 PR Newswire.
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