Source : Cell Therapeutics, Inc.
Systems Medicine, LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) , presented data from a preclinical study, which utilized RNA interference (RNAi) and bioinformatics to identify genetic markers - "contexts of vulnerability" - that enhance the anti-tumor response to the experimental drug candidate brostallicin, at the 2009 American Association for Cancer Research (AACR) annual meeting in Denver, Colorado. "Contexts of vulnerability" refers to the genetic configuration in a patient's tumor that makes it susceptible to a specific drug thus providing the genetic rationale for targeted therapy. The study's objective was to identify molecular determinants of brostallicin's anti-tumor response that could guide clinical development and drug combination studies by incorporating an integrated pharmacogenomics approach. The study was conducted by SM in collaboration with the Translational Genomics Research Institute's Pharmaceutical Genomics Division in Scottsdale, Arizona.
"This study has identified certain patient groups which might be more likely to benefit from therapy with brostallicin and have been invaluable in assisting us in identifying promising clinical development strategies for future development of this novel drug candidate," said Jack Singer, M.D., Chief Medical Officer of CTI. "Ultimately, we believe this approach should shorten the clinical development time and increase the success rate by bringing us closer to being able to offer the right drug to the appropriate patient."
Brostallicin is a small-molecule chemotherapeutic agent with a unique mechanism of action -- it binds to the minor grooves located in the DNA double helix. To identify genes associated with cellular response to brostallicin, a high-throughput RNA interference screen was performed in selected ovarian cancer cell lines. RNA interference is a cellular process that results in the targeted knockdown of specific genes. The current screen assayed the effect of over 7,000 individual gene knockdowns, representing the "druggable" genome, on brostallicin response.
The identified genes, representing unique contexts of vulnerability to brostallicin, converged on cellular concepts relating to DNA repair and chromosome modification. These findings were further extended and confirmed in breast cancer cell lines, wherein the knockdown of specific genes involved in these concepts, mentioned above, resulted in an increased response to brostallicin.
To substantiate the brostallicin response observed in the RNAi studies, drugs that target selected genetic targets were tested for synergistic activity in combination with brostallicin. The outcome of this validation work has identified important contexts and rational drug combinations that will be critical for the clinical development of brostallicin.
To review the poster and see more detailed information about the study, please go to http://www.celltherapeutics.com/investor_updates.
Brostallicin, a novel synthetic second-generation DNA minor groove binder, has shown 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 conducted by the European Organization for Research and Treatment of Cancer (EORTC).
About Systems Medicine (SM)
In July 2007, CTI acquired Systems Medicine, a privately held oncology company, in a stock-for-stock merger. SM applies a systems biology approach to drug development, combining pharmacogenomics and bioinformatics with experienced preclinical, clinical, and regulatory expertise to find and exploit a specific cancer's 'context of vulnerability.' Specifically, SM defines the molecular and genetic alterations (context) that cause cancer cells to be particularly sensitive (vulnerable) to a drug or combination of drugs--the "context of vulnerability."
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.
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This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of brostallicin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with brostallicin in particular, including, without limitation, the potential failure of the preclinical results to predict results in clinical trials, the potential failure of the clinical results to predict the safe and effective treatment of cancer, the potential failure of brostallicin to prove safe and effective for treatment of solid tumors particularly ovarian or colon cancers, determinations by regulatory, patent, and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing, and selling brostallicin, and the risk factors listed or described from time to time in the CTI's filings with the Securities and Exchange Commission including, without limitation, the CTI's most recent filings on Forms 10-K, 10-Q and 8-K. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Lindsey Jesch Logan
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