Kinase backgrounder: Iressa discovery part of major kinase project at Dana-Farber

Many times in military history, a sudden attack by a small, fast-moving force has broken an impasse and helped turn the tide against an entrenched foe. In such situations, timing is everything.

Dana-Farber researchers, sensing an opening in the cancer battle, are mounting a quick thrust to flush out suspected molecular cancer triggers in tumor cells. Drug companies can then select specific compounds that block these triggers, turning off the cells' stimulus to grow, but leaving normal cells unaffected.

The scientists are scanning the DNA from human tumor samples, sifting through their genetic blueprints for genes that produce abnormal growth-stimulating proteins known as tyrosine kinases. These mutant proteins behave like stuck "on" switches, causing unruly cell growth. The beauty of the plan, the investigators say, is that pharmaceutical companies have already developed hundreds of different drugs that inhibit tyrosine kinases, so they can quickly move these agents into clinical trials in humans. The approach could shave years off the customarily long delay between finding a vulnerable target in cancer cells and then testing new drugs to attack it.

Kinases are enzymes in cells that regulate their behavior, including when they should grow and when they should rest. Damaged kinases have been found in many types of cancer, where they spur the cells into runaway malignant growth. Many of those kinases belong to the group called tyrosine kinases. Of the 500 kinases in the human body, 94 of them are of the tyrosine type.

The new campaign was inspired by Dana-Farber research on tyrosine kinases in the 1980s and '90s that paved the way for the highly successful cancer drug Gleevec. It was among the first agents to take aim at specific mutant tyrosine kinases as a cancer therapy. Gleevec has stopped or shrunk tumors in many patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST), a disease that had been virtuall

Contact: Bill Schaller
Dana-Farber Cancer Institute

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