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Genes and biomarkers that allow doctors to choose the right therapy for the right patient

nts with colorectal tumors. For those with the mutations, the drug is likely to be inefficient and possibly harmful, according to researchers at France’s Institut National de la Sante et de la Recherche Medicale (INSERM).

"Because a variety of different effective agents may now be available for any given type of cancer, deciding which treatment regimen is likely to be the most effective and the least toxic is more complicated than ever," said Pierre Laurent-Puig, M.D., PhD, a professor of Oncology at University of Paris-Decartes. "Characterizing the factors that are predictive of toxicity and efficacy could lead to significant improvement in both the quality of treatment and outcomes."

Cetuximab, an antibody that attacks the ability of cells to respond to the epidermal growth factor, has been previously shown to be effective in treating metastatic colorectal cancer.

Dr. Laurent-Puig and his colleagues studied 114 patients who had been given cetuximab in combination with another drug, irinotecan.

According to the researchers, approximately 30 percent of patients may have a poor response to the drug. Almost none of the patients who responded to the drug had an activating KRAS mutation, as compared to 35 percent of the patients with stable disease or 55 percent of the patients with progressive disease.

According to Dr. Laurent-Puig, this might be due to the cascade of molecular interactions that occur after epidermal growth factor meets its receptor, EGFR. The KRAS enzyme is a key component to these molecular actions, but mutations in the KRAS gene could allow the enzyme to function whether or not it receives the commanding signal from EGFR. Therefore, the inhibition of EGF receptor by cetuximab will not block the molecular signals that are activated farther down the cascade.

The researchers also determined that KRAS mutations are independent of another predictive marker of cetuximab response, skin toxic
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Source:American Association for Cancer Research


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