Other targeted treatments act like the PARP inhibitor used to treat Denise Nichols: They cause cells to commit suicide. A drug used against multiple myeloma and other blood cancers, for example, causes malignant cells to die by preventing them from clearing out broken and malfunctioning proteins. Still others prevent the growth of new blood vessels that feed tumors. And some drugs combine two functions. One guides the molecule to pro-cancerous proteins, and a second contains some toxic element to kill the cancer cell.
Because drugs are still approved by regulators to treat specific diseases, not mutations alone, it's becoming important for doctors and patients to know what mutations in a tumor might make it responsive to a drug, even if the drug is not approved for that type of tumor. Fortunately, the technology for surveying hundreds of different genetic traits at once has become relatively cheap and easy to use within the past five years. So some leading cancer centers, including Massachusetts General Hospital, Memorial Sloan-Kettering in New York, MD Anderson in Houston, and Vanderbilt in Nashville, are now regularly using genotyping to hunt for glitches in many genes at once.
After Hammond, La., attorney Thomas Waterman, 63, was diagnosed with colon cancer in 2005, he underwent surgery, and later further surgery and chemotherapy when his cancer spread. This year, he enrolled in a clinical trial at MD Anderson in which sequencing of 50 genes from his tumor revealed a mutation in EGFR that might render his cancer vulnerable to a drug approved not for his disease but for lung and pancreatic cancer; he began taking the drug in May. Waterman's doctor at MD Anderson, Scott Kopetz, estimates that perhaps half of the patients enrolled in the trial so far are able to find nonstandard treatments to try. "What has changed this year is the realization that this is going to be the norm rather than the exception, and cancer centers will need to start programs that do this routinely," says José Baselga, chief of the division of hematology/oncology at Massachusetts General Hospital Cancer Center, where physicians screen patients' tumors for more than 150 cancer-causing mutations in some 20 genes. (They test in patients whose cancer has spread; people with contained tumors are often better served by surgery.)
A cancer patient whose hospital doesn't offer the screening can turn to private companies for genetic analysis. Foundation Medicine, based in Cambridge, Mass., reads out the entire genetic sequence of nearly 200 genes from a patient's tumor to discover telltale signs that her cancer might respond to approved or experimental targeted treatments. The company says that it has found an average of about three clinically relevant genetic glitches in each of the 400 patients whose tumors it had analyzed as of early summer. The test costs $5,800, though Foundation Medicine president and chief executive Michael Pellini says it is sometimes covered by insurance.
Immune system boosters. For some cancers, there are no treatments yet that target particular genetic mutations, and many patients don't have a mutation known to respond to a drug. That was the position that Valerie Esposito, now 41, found herself in four years ago. Esposito, a Long Island, N.Y., mother of three, was first diagnosed with melanoma in 2004 and had surgery to remove a tumor from her back. In 2008, doctors noticed that her cancer had spread to her lungs and spleen. Surgery and chemotherapy proved fruitless.
So Esposito's doctors at Memorial Sloan-Kettering offered her an experimental drug, ipilimumab, one of a class of new treatments that boost a patient's own immune defenses against cancer rather than attacking the cancer itself. Esposito began taking ipilimumab in the fall of 2009. Her tumors stayed about the same size for a year and a half; then, a few months after radiation therapy to treat a painful tumor pressing on her spine, all of her tumors but one shrank away. "I had just come home from getting a CAT scan, and I didn't even make it in the front door of my house before my doctor was calling and telling me the good news," recalls Esposito, whose spinal tumor has also stopped growing. Last year, regulators approved ipilimumab after clinical trials found that it was the first treatment ever to prolong the lives of patients with advanced melanoma.