Moving Target: Why a Cancer 'Cure' Is So Elusive

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In the realm of targeted cancer treatment, Carla Leslie is a success story.

Leslie was diagnosed in September of 2010 with Stage 3C breast cancer, a disease that kills 50 to 60 percent of those who have it within five years. She was treated at MD Anderson Cancer Center in Houston with chemotherapy plus Herceptin, a drug that targets a specific genetic mutation in certain kinds of breast cancer. The results were remarkable; Leslie is now in remission.

"It was unbelievable, it was truly unbelievable," she said. "My experience with the treatment was beyond anything I could have expected."

Stories like Leslie's are becoming more common. Yet, as any doctor will tell you, even today the prospect of a cure for most kinds cancer is elusive. Doctors have had some success using drugs like Herceptin, which tailor a patient's treatment to their specific genetic makeup. This practice, known as "personalized medicine," is an effective approach in some cases. But the cancers that cannot be treated with these personalized approaches -- in other words, most of them -- are so complex that any simple approach to treating them remains elusive, at least for now.

New research, published Wednesday in the New England Journal of Medicine, reinforced this idea, demonstrating that the tumor cells of a particular kind of cancer can vary not only throughout a particular patient's own body, but even within a single tumor. Each of these different variations of the same kind of cancer cell is known as a mutation, and each of these mutations can be thought of like a target. So while a given treatment might hit some of these targets, others are left unscathed, and the cancer remains.

In this study, researchers took multiple samples of tumors from four patients with a kind of cancer originating in the kidneys called metastatic renal cell carcinoma. By analyzing these samples, they found that cancer cells within a single tumor and at places where the cancer had spread showed a large amount of variation, with 60 percent of tumor mutations not uniformly detected in every part of the tumor. This has implications not only for treatment, but for diagnosis as well. In some cases, the researchers found mutations associated with both good and bad prognosis in different parts of the same tumor.

The variation among tumor cells might actually help cancer to survive and could explain why some cancers become resistant to chemotherapy.

These findings highlight new challenges in the management of cancer and suggest that, in many cases, the idea of "personalized medicine" might be too simplistic for cancer treatment.

"There might be concern that the personalized medicine story has created a false sense of hope," said Dr. Amy Abernethy, director of the Duke Cancer Care Research Program in Durham, N.C. "I don't think that it is false hope, but rather a false sense of the simplicity."

Although this might cast some doubt on gene-specific therapies, most physicians are optimistic that this information will lead to advancements for improved cancer treatments.

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