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National Cancer Institute Research Identifies Unique Mechanism of Brostallicin's Anti-Tumor Effectiveness
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Cell Therapeutics (CTI) announced that researchers from the Laboratory of Molecular Pharmacology at the National Cancer Institute presented new preclinical research identifying unique anti-tumor mechanisms of brostallicin that sets this agent apart from other currently used chemotherapy agents.
CTI acquired worldwide rights to brostallicin when it acquired privately-held Systems Medicine LLC in 2007. Published in the journal Molecular Cancer Therapy, the researchers utilized preclinical studies to provide clues into tumor susceptibility mechanisms for brostallicin, a synthetic DNA minor grove binder, and to identify differences between brostallicin and trabectedin, which is a natural marine product approved in Europe.
Unlike other chemotherapy agents, including trabectedin, the NCI research indicates that the tumor cell DNA damaging effects of brostallicin are enhanced by high tumor glutathione levels, a hallmark of drug-resistant tumors.
Brostallicin was shown to affect DNA in both dividing and quiescent cells. Its actions can be followed by induction of a specific DNA binding protein foci that can be detected in circulating blood cells. Importantly, brostallicin was active in a trabectedin-resistant cell line.
"These preclinical data provide important further insights into the specific bio-marker (tumor glutathione levels) that increases the probability of achieving improved anti-tumor effectiveness by careful selection of patients who are most likely to benefit, and is consistent with our focus on personalized approaches to cancer drug development," said Jack Singer, M.D., Chief Medical Officer at CTI.
"This may be of particular importance in patients with relapsed 'triple-negative' breast cancer, ovarian, or colorectal cancer following treatment with platinum containing regimens where high glutathione levels are associated with chemotherapy resistance."
CTI acquired worldwide rights to brostallicin when it acquired privately-held Systems Medicine LLC in 2007. Published in the journal Molecular Cancer Therapy, the researchers utilized preclinical studies to provide clues into tumor susceptibility mechanisms for brostallicin, a synthetic DNA minor grove binder, and to identify differences between brostallicin and trabectedin, which is a natural marine product approved in Europe.
Unlike other chemotherapy agents, including trabectedin, the NCI research indicates that the tumor cell DNA damaging effects of brostallicin are enhanced by high tumor glutathione levels, a hallmark of drug-resistant tumors.
Brostallicin was shown to affect DNA in both dividing and quiescent cells. Its actions can be followed by induction of a specific DNA binding protein foci that can be detected in circulating blood cells. Importantly, brostallicin was active in a trabectedin-resistant cell line.
"These preclinical data provide important further insights into the specific bio-marker (tumor glutathione levels) that increases the probability of achieving improved anti-tumor effectiveness by careful selection of patients who are most likely to benefit, and is consistent with our focus on personalized approaches to cancer drug development," said Jack Singer, M.D., Chief Medical Officer at CTI.
"This may be of particular importance in patients with relapsed 'triple-negative' breast cancer, ovarian, or colorectal cancer following treatment with platinum containing regimens where high glutathione levels are associated with chemotherapy resistance."
