Skin cancer drug hopes raised by study

A new treatment for advanced skin cancer almost doubles survival times, according to an international study.

Melanoma is aggressive and dangerous

Doctors say 132 patients in the US and Australia who were given the drug vemurafenib gained several extra months of life.

Research in the New England Journal of Medicine found those in the study lived an average of 16 months, compared with nine months on conventional treatment.

Vemurafenib (Zelboraf) has been approved for use in Europe.

The treatment is one of two drugs for late-stage melanoma, approved on fast-track in the US last year, which offer hope for patients with advanced melanoma.

Before that, there had been no new drugs for the cancer for more than a decade.

         Malignant melanoma

• Melanoma, also called malignant melanoma, is a type of skin cancer that is aggressive and dangerous
• Melanoma is relatively rare and makes up 10% of all skin cancer cases
• Melanoma is responsible for most deaths due to skin cancer
• About 2,000 people die every year in England and Wales from melanoma
• The main cause of melanoma is believed to be over-exposure to the sun
• Over using sunbeds and sun lamps may also increase the risk of developing melanoma

Vemurafenib is suitable for about half of patients with advanced melanoma as it targets tumours that express a certain gene mutation.

Dr Antoni Ribas, a professor of haematology/oncology and a researcher at the Jonsson Cancer Center at the University of California-Los Angeles, said: «This study shows that Zelboraf changes the natural history of this disease. This data is beyond what I would have expected.

«We’re seeing a significant number of patients with durable responses to the drug, and that the whole group of treated patients is living longer.

«These results tell us that this drug is having a very big impact, and this changes the way we treat metastatic melanoma.»

According to the European Medicines Agency, the drug has been recommended for approval in Europe, pending final authorisation by the European Commission.

Elizabeth Woolf, head of Cancer Research UK’s information website Cancer Help UK, said: «This is an interesting, impressive but relatively small trial of a promising new-generation melanoma drug, which Cancer Research UK is proud to have played a role in developing.»

But she said there were still questions that remain unanswered, not least the cost.

We’re getting somewhere with these targeted drugs but we have a whole raft of research still to do address the issue of resistance”

Kate Law. Cancer Research UK

«Everyone on the trial had the drug, so we cannot tell how large the benefits are, compared to people who didn’t have it, or had another treatment. And because the drug targets a particular gene fault, only half of all melanoma patients are eligible.

«About half of those treated seem to benefit, so it could potentially help roughly a quarter of patients with advanced melanoma overall.

«Looking at these uncertainties, and now that the drug is available to UK cancer patients, it will be interesting to see what price the manufacturer charges so as not to place too great a strain on already scarce NHS resources.»

Drug resistance

Cancer Research UK said once the drug was licensed in Europe, patients would be able to discuss treatment options with their doctor.

In England, patients will have to apply to the Cancer Drugs Fund, the charity said.

Kate Law, director of clinical and population research at Cancer Research UK, said the treatment was one of a new generation of cancer drugs targeted at patients with a specific genetic make-up.

While it offered hope, she said, it was not a cure as the cancer eventually became resistant to the drug.

She told the BBC: «This is not a cure – you’re talking an extra six months of life.

«We’re getting somewhere with these targeted drugs but we have a whole raft of research still to do to address the issue of resistance.»

Bbc.co.uk [en línea] Londres (UK): bbc.co.uk, 27 de febrero de 2012 [ref. 23 de febrero de 2012] Disponible en Internet: http://www.bbc.co.uk/news/health-17128925

Transforming Drug Development

Taking aim at the alarming slowdown in the development of new and lifesaving drugs, Harvard Medical School is launching an  Initiative in Systems Pharmacology, a comprehensive strategy to transform drug discovery by convening biologists, chemists, pharmacologists, physicists, computer scientists and clinicians to explore together how drugs work in complex systems.

“With this Initiative in Systems Pharmacology, Harvard Medical School is reframing classical pharmacology and marshaling its unparalleled intellectual resources to take a novel approach to an urgent problem,” said Jeffrey S. Flier, dean of the Faculty of Medicine at Harvard University, “one that has never been tried either in industry or academia.”

Modern drug discovery has focused on the interaction between a candidate drug and its immediate cellular target. That target is part of a vast and complex biological network, but because studying the drug in the context of a living system is profoundly difficult, scientists have largely avoided this approach.

As a result, predicting the effects of a particular candidate drug in humans is currently all but impossible, and many initially promising drugs have been found to lack efficacy or to have unsupportable levels of toxicity—typically at a late stage of a clinical trial, at a cost of years of effort and up to $1 billion.

“Right now in the world of drug discovery, it’s as if we have a map of a highway system that only contains small pieces extending a few miles here and there, without any connectivity on a large scale,” said Marc Kirschner, the John Franklin Enders University Professor of Systems Biology and chairman of the HMS Department of Systems Biology. “If you try to plan a trip on such fragmentary information, you’ll fail. It’s our inability to develop a coherent picture that has stymied drug discovery for so long.”

As drug makers exhaust the most promising candidate areas, the number of new drugs brought to patients has actually decreased in recent years, even as the cost of discovery has soared.

A better understanding of the whole system of biological molecules that controls medically important biological behavior, and the effects of drugs on that system, will help industry identify the best drug targets and biomarkers. This will help to select earlier the most promising drug candidates, ultimately making drug discovery and development faster, cheaper and more effective.

“Through this new initiative, we will develop large-scale models of biological systems and networks which should more accurately predict drug efficacy,” Kirschner added.

The systems approach

The science of analyzing specific biological processes within the context of an entire living system, called systems biology, is relatively new. Harvard Medical School is a world-leader in this area, having established one of the first department-level programs in 2003.

Building on this success, Harvard’s new effort will apply systems biology’s innovative approaches to the understanding and prediction of drug activity, drawing on the vast range of biomedical expertise available at the medical school and its affiliated teaching hospitals and research institutes.

Led by Kirschner and systems biology professors Peter Sorger and Tim Mitchison, the Initiative in Systems Pharmacology will include faculty from a broad array of disciplines: systems biology, cell biology, genetics, immunology, neurobiology, pharmacology, medicine, physics, computer science and mathematics. The initiative will be fueled by a strong and diverse group of existing faculty and new recruits who will be based in several departments, and will be supported by an ambitious fundraising effort.  New approaches could include use of chemical biology to develop probes of biological pathways and failure analysis on unsuccessful drugs, similar to how the aviation industry scrupulously analyzes accidents to learn what went wrong. Such a practice is not common in today’s pharmaceutical industry.

Other projects currently underway at HMS will be expanded through the new initiative.

For example, Sorger and Mitchison collaborate with Ralph Weissleder, HMS professor of radiology and director of the Center for Systems Biology at Massachusetts General Hospital, to probe the mechanism by which anti-cancer drugs kill tumor cells in patients and thereby make the effects of treatment more predictable.  “What’s amazing is how little we know even about many drugs that work,” Sorger said. “A systems approach could help tailor existing treatments to specific patients, and find new uses for therapies we already have.”

And in the lab of systems biology professor Roy Kishony, scientists research the evolutionary forces that shape the emergence of antibiotic-resistant bacteria, seeking strategies for developing combination therapies to slow or reverse the spread of drug resistance.

The initiative will also include a new educational program, one that develops a new generation of students, postdoctoral fellows and physician-scientists. The goal is to train future leaders in academic and industrial efforts in systems pharmacology and therapeutic discovery.

Transforming therapeutics

The Initiative in Systems Pharmacology is a signature component of an HMS Program in Translational Science and Therapeutics. There are two broad goals: first, to increase significantly our knowledge of human disease mechanisms, the nature of heterogeneity of disease expression in different individuals, and how therapeutics act in the human system; and second—based on this knowledge—to provide more effective translation of ideas to our patients, by improving the quality of drug candidates as they enter the clinical testing and regulatory approval process, aiming to increase the number of efficacious diagnostics and therapies reaching patients.

“Systems pharmacology is the first and a key pillar of Translational Science and Therapeutics at Harvard Medical School,” said William Chin, the Bertarelli Professor of Translational Medical Science, executive dean for research at HMS and former head of research for Eli Lilly & Co.

“We intend to harness all the strengths of HMS to gain a deeper understanding of the cause and nature of disease, addressing some of the most vexing questions that continue to impede the development of new drugs,” Chin said. “We will focus our strengths and resources to translating such knowledge into new classes of life-saving medicines.”

Focushms.com [en línea] Boston (USA): focushms.com, 17 de octubre de 2011 [ref. 17 de octubre de 2011] Disponible en Internet:

http://www.focushms.com/features/transforming-drug-development/