Surviving Cancer

Two years ago, Louise Jacobs was idly playing with a necklace when she felt a couple of tiny lumps around her collarbone. She thought they were calcium deposits. She was wrong. Jacobs had advanced lung cancer that had already spread to her lymph nodes. Because the tumors had infiltrated healthy tissue, surgery was not an option. "It was devastating," says the teacher, 56, from Atlanta. "I never smoked, my husband never smoked, and nobody in my immediate family had ever had cancer."

Jacobs immediately started the only treatment doctors had to offer--attacking the tumors with intensive chemotherapy and radiation to try to kill the malignant growths. For seven weeks, her body was bombarded with radiation twice a day and poisoned with toxic chemotherapy drugs once a week.

One year later, Jacobs got the bad news that cancer was starting to grow again in her lungs. This time, however, the doctors had something else to offer. Two new anticancer drugs that target cancer cells more precisely and with less toxicity had been approved by the FDA. (Two more have since been approved.) Jacobs' doctors at the M.D. Anderson Cancer Center in Houston enrolled her in a clinical trial for a combination of two of those agents, Tarceva and Avastin, last August. "The difference is like night and day," says Jacobs. "I take a pill every day, and every three weeks I go in for an infusion, which takes about 30 minutes." After nearly a year on the experimental cocktail, she has seen her primary lung cancer shrink more than 50%.

Jacobs is part of an exciting vanguard--the first wave of cancer patients who are benefiting from a more targeted, molecular-based assault on the disease. Old-fashioned chemotherapy and radiation treatments were blunt weapons that killed healthy cells along with malignant ones; the treatments were far too toxic for most patients to endure. By comparison, the new-generation drugs are precision-guided missiles that zero in on tumors with a minimum of collateral damage. Used in combination with advanced techniques for classifying tumors by their molecular signatures and screening patients by their DNA, the drugs are transforming cancer from a deadly disease into a chronic condition that can be managed indefinitely. The FDA, responsible for approving new drugs, acknowledged the trend earlier this year when it issued new guidelines for evaluating this type of molecular and genetic data. "The bench and bedside have merged," says Dr. Roy Herbst of M.D. Anderson Cancer Center. "We are truly in the molecular-targeted era."

After years of feeling that they were losing the war on cancer, doctors and researchers gathered at the American Society of Clinical Oncology meeting in New Orleans reported last week that they finally have a deep enough understanding of the molecular underpinnings of cancer to offer patients new hope. "The paradigm is changing," says Dr. David Sidransky, a cancer specialist at Johns Hopkins Medical Institution. "New targeted drugs are coming, and we have to figure out how to use them."

IDENTIFYING MUTATIONS