Joining forces to target more tumors
How wide is the field for new cancer drugs? Consider this: Of all the possible targets on a tumor cell – the hundreds or thousands of genes that drive its growth and delay its death – only about 20 percent are reachable with existing varieties of drugs.
"There are essentially two classes of drugs," says Greg Verdine, PhD, who directs the Chemical Biology Initiative at Dana-Farber and is the Erving Professor of Chemistry at Harvard. "The first are small molecules that bind to 'greasy pockets' on the target and deactivate it. Their small size gives them the ability to hit targets both outside and inside the cell, but prevents them from binding firmly, making them somewhat ineffective.
"The second type are 'biologicals.' They're large proteins that have an almost unlimited targeting ability – they don't need pockets to bind to – but they have bad geography. They're unable to get into cells."
These shortcomings are so pronounced that no drugs exist for two of the genes most commonly mutated in cancer, K-Ras and c-Myc.
One solution is to use advanced technology to create artificial compounds that are neither small molecules nor biologicals, but some combination. That is one goal of Dana-Farber's new effort in chemical biology (see story in the Spring/Summer 2007 Paths of Progress).
"With chemical biology, it may be possible to synthesize substances that can penetrate cells and have large surface areas for binding," Verdine says. "This is an area where academic science has to be the leader; private companies generally can't attract venture capital for doing this kind of high-risk, high-reward work.
"What's unique about our program is that it represents a collaboration between one of the best chemistry departments in the world (Harvard's) and a top research-based cancer center," he adds. "In the three years since the program began, we have established a position as a leader in developing new targeting technologies."
