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'Master switch' experimental drug could treat different cancers

2012-07-11 06:52:09

A UNIQUE multi-target experimental drug could treat a range of cancer types, according to research published in Clinical Cancer Research* today (Tuesday).

Cancer Research UK-funded work at The Institute of Cancer Research in London shows that AT13148** – a type of drug called a kinase inhibitor – operates like a master switch to simultaneously block several different enzymes that control cancer cell growth and cell death.

Many kinase inhibitors have been developed that block only a single enzyme, but so far these drugs have shown only limited effectiveness. Scientists hope that switching off cell signals at multiple points could make the drug more likely to benefit patients and also delay drug resistance.

Laboratory tests showed that AT13148 was able to kill a range of cancer cell types including sarcoma, breast and prostate.

Lead author Dr Michelle Garrett, team leader in the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, said: “Our study shows that this drug is effective against a range of tumour types, and operates by blocking multiple targets. These promising results have led to the decision to take the drug into patient trials.”

The molecule was originally discovered by scientists on the PKB drug discovery programme, a collaboration between Astex Pharmaceuticals, Cancer Research Technology and The Institute of Cancer Research, which ran from 2003 through to 2006. The collaboration generated a series of compounds, of which a preferred candidate was then selected.

Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: “This is exciting research showing that this experimental drug does the job of several drugs all at once, by targeting numerous weak spots in cancer cells.

“Using one master switch to turn off the different faulty messages forcing cancer cells to keep growing could be an effective way to destroy tumours. It could also reduce the chance of patients becoming resistant to treatment."

Notes to Editors:

*AT13148 is a novel, oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumour activity. Clinical Cancer Research. Yap et al.
**The experimental drug is owned by Astex Pharmaceuticals.

About Astex Pharmaceuticals
Astex Pharmaceuticals, Inc. is an international, NASDAQ-listed (ASTX) pharmaceutical company dedicated to the discovery and development of novel therapeutics with a focus on oncology. Astex Pharmaceuticals was formed out of a merger between SuperGen and Astex Therapeutics with locations in Dublin, CA and Cambridge, UK. 
Astex Pharmaceuticals receives significant royalties on global sales of Dacogen® (decitabine) for Injection, a marketed drug developed by the company. Eisai and Janssen, the global marketers of Dacogen, have filed for approval of a new Acute Myeloid Leukaemia indication in the EU.
Astex Pharmaceuticals has a broad portfolio with four clinical programs that are expected to provide phase II proof-of-concept data in 2012. Two of the programs, AT13387, an HSP90 inhibitor, and SGI-110, a second generation hypomethylating agent, will be expanded in 2012 to test clinically additional indications. Astex has partnered development programs and on-going collaborations with pharmaceutical companies including J&J, GSK, AZ and Novartis that could generate more than a billion dollars in milestone revenue as products and projects progress.
Astex is a recognized world leader in fragment-based drug discovery and uses its proprietary technologies to generate new drug candidates across multiple therapeutic indications. The fragment-based approach to drug discovery has been shown to be successful at identifying small molecules with optimal drug-like properties against difficult targets. 
For more information about Astex Pharmaceuticals: http://www.astx.com.

The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes.
Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk

Notes to editors