The Hindu : Front Page : Cancer: path cleared for drugs

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Saturday, Aug 15, 2009
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Cancer: path cleared for drugs

Nicholas Wade

NEW YORK: A team, led by Dr. Piyush B. Gupta at the Broad Institute, a Harvard-MIT collaborative for genomics research, has discovered a way to identify drugs that can specifically attack and kill cancer stem cells.

Another approach to concentrating on cancer stem cells, based on the use of antibodies, was reported this month by OncoMed Pharmaceuticals, a company founded by Dr. Michael F. Clarke, a Stanford researcher who in 2003 discovered cancer stem cells in breast tumours.

If effective drugs against cancer stem cells can be developed, one obvious strategy would be to use them in combination with standard chemotherapeutic agents, so that all types of cells in a tumour could be attacked. In that way, cancer would be attacked as AIDS is now — with a cocktail of chemicals that blocks all escape paths.

Both the AIDS virus and cancer cells can change their DNA to dodge an effective drug, but are thought to perish if confronted with many drugs at the same time.

Standard chemotherapy is often effective because the chemicals are applied in such large doses that they kill all cells. But this scorched-earth approach is stressful for the patient.

“You could probably lower the doses considerably with a combination of drugs that attacked specific types of cell,” said Dr. Gupta.

Dr. Eric S. Lander, director of the Broad Institute, said: “If we make a drug that kills 99.9 per cent of the cells in a tumour but fails to kill the 0.1 per cent, that is the real problem. It’s a pyrrhic victory.”

Dr. Lander said given the new drug screening system and the idea of using combinations of drugs against cancer, there was “a potential for a real renaissance in cancer therapeutics”.

“We have not been able to do that yet with cancer,” he added, “but if we could, it’s a numbers game, and we win.”

The theory has been thrust into the spotlight in the last five years with the discovery of stem cells in many types of solid tumours, including those of the breast, brain, prostate, colon and pancreas. This month, a Stanford team led by Irving Weissman reported finding the stem cells of bladder cancer.

But the theory is not without critics. “The cancer stem cell hypothesis has in the past year been challenged on many fronts,” said Dr. Bert Vogelstein, a leading cancer geneticist at Johns Hopkins University. “For example, a paper on melanomas last year showed that 100 per cent of melanoma cancer cells were cancer stem cells.” If many of a tumour’s cells are stem cells, then existing chemotherapy agents are clearly killing them, said Dr. Vogelstein, and the cancer stem cell theory is not an effective guide to finding new drugs. The theory has also aroused opposition because, in its extreme version, it implies that standard chemotherapy goes after the wrong targets and is ineffective. “It’s the most amazing polarity that I’ve seen,” said Dr. Clarke . “It’s like two religions fighting.” — © 2009 The New York Times News Service

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