Cancer drug development guided by genomics
SAN DIEGO, April 14 /PRNewswire-FirstCall/ -- Systems Medicine LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) (Nasdaq and MTAX: CTIC), presented data from a preclinical study identifying the genetic markers in patients more likely to respond to treatment with the experimental drug, brostallicin, at the 2008 American Association for Cancer Research (AACR) annual meeting. These findings will be used to guide future development of brostallicin by suggesting which patients are most likely to respond when treated with brostallicin, potentially making the drug's development more efficient. This method of drug development is known as the context of vulnerability approach. The study was co-directed by Jeffrey A. Kiefer, Ph.D., and Holly Yin, Ph.D. in the Translational Genomics Research Institute's Pharmaceutical Genomics Division located in Scottsdale, Arizona.
"This study is an example of using a pharmacogenomic screening approach to find insights that guide the selection of specific contexts of vulnerability for brostallicin. These results provide information on which genetic characteristics to look for in determining whether or not a patient might benefit from treatment with brostallicin. In SM and CTI's continued efforts to make cancer more treatable, results like these broaden our knowledge of brostallicin's context of vulnerability, and bring us closer to being able to offer the right drug to each patient," said Jeffrey Jacob, CEO of SM.
In the study, the NCI-60 cell line panel was profiled for brostallicin response and correlated with specific genomic information derived from the cell line panel. The NCI-60 is a group of 59 human cancer cell lines derived from tumor tissue -- brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate, and skin. Scientists often use cell lines, also called models, in preclinical studies in a laboratory setting. The information learned from preclinical studies helps guide the design of future clinical trials. An integrative knowledge mining strategy was used to identify the genomic and functional consequences of brostallicin response. According to the study abstract, "Gene Set Enrichment Analysis (GSEA) revealed unique associations between cells' sensitivity to brostallicin," and distinct sets of genes, "including significant associations with particular aspects of DNA repair." In addition to correlative genomic analyses on the NCI-60 cell line panel, a high-throughput siRNA (HT-RNAi) screen was conducted to functionally identify those gene products involved in brostallicin response. RNA interference is an experimental technique that allows for the targeted reductions of gene expression. A systematic evaluation of 7,000 genes was conducted in a cisplatin resistant variant of the ovarian cancer cell line A2780. A number of interesting 'hits' or targets were identified in the screen that modulate the cells sensitivity to brostallicin and represent unique and functionally based contexts of vulnerability. Knowledge mining of the brostallicin siRNA gene hits revealed enrichment of a number of important molecular concepts and important genes involved in DNA repair. On the basis of these and related studies, a clinical trial will soon be initiated specifically targeting patients with genetic defects in mismatch repair genes such as BRCA1 and 2, which are associated with susceptibility for breast and ovarian cancer.
To review the poster and see more detailed information about the study, please go to http://www.celltherapeutics.com/investors_news-updates.htm.
Context of Vulnerability
CTI and SM are employing a new method of drug development, the "context of vulnerability" approach. Using cutting-edge genomic profiling tools, the Company creates a profile of which cells react to certain drugs in an effort to discover cells' vulnerabilities (weak spots) and where the drugs are the strongest. With these data, investigators can target those patients with the highest probability of benefiting from a particular drug. By treating only the patients with the genetic characteristics known to react well to the drug, scientists may be able to decrease the time and money necessary to develop a drug and bring it to market. This approach also has the potential to improve the rate of treatment success and increase the number of approved drug products across the drug development industry.
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 conducted by the European Organization for Research and Treatment of Cancer (EORTC).
About Systems Medicine (SM)
In July 2007, CTI acquired Systems Medicine (SM), 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 make cancer cells 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 http://www.CellTherapeutics.com.
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 brostallicin to
prove safe and effective for treatment of solid tumors, 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 Company's filings with the Securities and Exchange Commission
including, without limitation, the Company's most recent filings on Forms
10-K, 8-K, and 10-Q. 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.
|SOURCE Systems Medicine LLC|
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