For a preview of how genomics will change cancer medicine, consider the impact that gene-targeting therapies are already having in lung cancer treatment. When a patient with non-small cell lung cancer – the most common form – comes to Dana-Farber, a sample of his or her tumor is analyzed for mutations in five genes (EGFR, KRAS, BRAF, EBBR2, and PIK3CA) and for a "translocation," or misplacement, of another gene (EML4-ALK). If tests reveal a mutation in EGFR, patients often receive the drug Tarceva, which blocks the EGFR protein's actions and can extend lives by up to three years if the cancer has not spread to the brain – twice the expectancy of conventional treatment. If a tumor tests positive for any of the five other abnormalities, patients can enroll in clinical trials of research drugs that specifically address the problem genes. This matching of therapies to a tumor's specific genetic defects is the essence of what is coming to be known as personalized medicine.
The new protocol marks a decisive turn. "Ten years ago, a study compiled the results of all the clinical trials of lung cancer drugs over the previous 20 years. Only five of those trials showed any benefit," recounts Bruce Johnson, MD, director of Dana-Farber's Lowe Center for Thoracic Oncology. "During that period, the median survival period for patients with advanced disease increased by just two months."
As a group, the six genetic irregularities screened at Dana-Farber account for a relatively small percent of lung tumors. EGFR mutations occur in about 12 percent of non-small cell lung cancers, while each of the other gene mutations is found in 2 to 5 percent of cases. But because the total number of non-small cell lung cancer patients is so large – 220,000 people are diagnosed with the disease annually in the United States – even 2 percent translates into approximately 4,000 individuals.
"It's become clear that the chances of finding a single abnormality in non-small cell lung cancer that could be targeted with a drug are quite low," says Johnson. "Developing targeted therapies for the disease needs to be done a few percentages at a time."
With research, those percentages are adding up quickly. Together, clinical trials now under way at Dana-Farber cover nearly a quarter of all non-small cell lung cancer. "Our goal is to have targeted therapies available for half these cases in the next decade," Johnson asserts.
Paths of Progress Spring/Summer 2011 Table of Contents
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