Navigation Links
New Gene Discovery Suggests Which Patients CTI's Brostallicin May Benefit
Date:4/13/2008

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.

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 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.

Media Contact:

Lindsey Jesch

T: 206.272.4347

F: 206.272.4434

E: media@ctiseattle.com

http://www.celltherapeutics.com/media.htm

Investors Contact:

Leah Grant

T: 206.282.7100

F: 206.272.4434

E: invest@ctiseattle.com

http://www.celltherapeutics.com/media.htm


'/>"/>
SOURCE Systems Medicine LLC
Copyright©2008 PR Newswire.
All rights reserved

Related medicine technology :

1. Intra-Cellular Therapies Announces the Discovery of Potent Antidepressant Activity in ITI-007
2. Intra-Cellular Therapies Announces the Discovery of Potent Antidepressant Activity in ITI-007/ITI-722
3. Ono Enters into a New Fragment-Based Drug Discovery Agreement with Evotec
4. deCODE Launches a DNA-Based Test for Assessing Risk of Prostate Cancer on the Back of the Discovery of New Prostate Cancer Genes
5. FASgen Announces a New Discovery in Obesity Research
6. Orion Genomics Announces the Discovery of Novel Breast Cancer Biomarkers
7. Nobel Prize-Winning Discovery
8. FASgen Announces New Discovery for Treatment of Stroke
9. Ambrx Enters FGF-21 Type 2 Diabetes Drug Discovery Collaboration with Merck and Co. Inc.
10. Five Clinical Studies to Receive $2.5 Million Under Foundations 2007 Clinical Discovery Program
11. ARCA Discovery Announces Data Demonstrating Potential for Bucindolol as Targeted Therapy in Heart Failure, Atrial Fibrillation, and Ventricular Arrhythmia
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)...  The ALS Association, in partnership with ALS Finding a ... a biomarker to track TDP43 aggregation. The successful team(s) with ... million investment. --> --> ... cells in the brain and the spinal cord. Eventually, people ... movement, which often leads to total paralysis and death within ...
(Date:2/10/2016)... 2016 Puerto Rico Healthcare and Life ... Healthcare and Life Sciences Report 2016 . --> ... Rico Healthcare and Life Sciences Report 2016 . ... largest territory in the world for pharma manufacturing, a territory ... manufacturing, and more universities per square mile than anywhere else ...
(Date:2/10/2016)... 2016  Visage Imaging Inc. ("Visage"), a wholly ... announced that the American College of Radiology (ACR) ... the Visage 7 Enterprise Imaging Platform as the ... Imaging SIMulation (SIM). SIM is the assessment component ... a multi-faceted and fully-integrated online assessment, education and ...
Breaking Medicine Technology:
(Date:2/10/2016)... ... ... Early this week, Team Iconic at J. Walter Thompson and Nestlé KITKAT ... global confectionery brand sourced from 100% sustainable cocoa. , The Nestlé Cocoa Plan aims ... activities that focus on better farming, better lives and better cocoa. In order to ...
(Date:2/10/2016)... PA (PRWEB) , ... February 10, 2016 , ... As ... offer two webinars in February 2016. Each webinar features a dynamic expert and ... to benefit their athletes, patients and facilities. Both events are free to attend, ...
(Date:2/10/2016)... ... ... Emergency rooms provide emergency care to stabilize critical health issues, but emergency ... emergencies at risk of losing a tooth or their smiles. Dr. Marine Martirosyan, ... emergencies include:, , Avulsed or knocked-out teeth , ...
(Date:2/10/2016)... St. Louis, Missouri (PRWEB) , ... February 10, ... ... 11-14, 2016, in San Diego, will bring together more than 200 of the ... in healthcare for the future. , “The true benefit of the Forum is ...
(Date:2/10/2016)... ... ... AHRA: The Association for Medical Imaging Management announced today ... as keynote speaker at the organization’s 2016 Spring Conference. Fox’s topic, Lead with ... with their own organizational staff and leadership. , “I am so excited ...
Breaking Medicine News(10 mins):