Hitting the bull’s-eye

Targeted cancer therapies begin making their mark

Leigh MacMillan, Ph.D.
Published: February, 2007

Colorized X-ray of a lung tumor
Zephyr/Photo Researchers, Inc.
Alan Sandler, M.D., pulls up a slide on his computer screen that shows—in schematic fashion—the signaling pathways inside a malignant cell. At a glance, it looks hopelessly complicated. White arrows indicate the chain of communication between proteins; the arrows point here and there, crisscrossing the cell like strands of spaghetti left on a plate.

“I’ll give you a minute to jot this down,” Sandler quips, adding that this line draws chuckles when he uses it during lung cancer seminars.

The image is actually an oversimplification of the molecules and pathways that “drive” the cancer cell and which are targets for the newest generation of anti-cancer drugs. Seventeen blue boxes on the slide list 29 different “targeted therapies” that are already approved or still in development, and where in the cell they act.

“The explosion of new drugs that are out there to study in cancer is astonishing,” says Sandler, associate professor of Medicine and medical director of the Thoracic Oncology program at the Vanderbilt-Ingram Cancer Center. He recalls that in 1992, when he finished his fellowship, it was common not to even give chemotherapy to patients with metastatic non-small cell lung cancer because the benefit was still questionable.

Today, chemotherapy and targeted agents are extending life and offering hope to these very same patients.

“These are really exciting times in cancer therapy, especially for lung cancer,” says David Carbone, M.D., Ph.D., Harold L. Moses Professor of Cancer Research at Vanderbilt-Ingram. “Ten years ago we had extremely limited options.” Today, some of the new targeted therapies are “nearly miraculously effective.”

Carbone cites the effects of the drug imatinib (Gleevec) in patients with chronic myelogenous leukemia and gastrointestinal stromal tumors, and the drug erlotinib (Tarceva) in select lung cancer patients. “It’s like a Lazarus response,” he says.

But as the number of new drugs climbs, so do the challenges in designing clinical trials to test the new therapies, selecting the patients who will most benefit from them, managing the costs of these drugs—thousands of dollars per month—and moving forward to develop drugs aimed at different targets in the cancer cell.

A rare leukemia’s lesson

The concept of a “magic bullet” to treat disease dates to the late 19th century. Nobel laureate Paul Ehrlich, M.D., coined the term in reference to compounds that would seek out and destroy pathogenic microbes without harming the patient.

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