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Mutations in Gene family Affect Response, ADRs in New Colorectal Cancer Regimen


Researchers from the Fox Chase Cancer Center in Philadelphia have identified serum genetic markers that may help physicians predict the way a patient with colorectal cancer will respond to irinotecan.

“Our data suggest that variations in genes that help metabolize irinotecan may be useful predictors of how well colorectal cancer patients respond to this drug and how severe side effects will be,” according to Leslie Carlini, a research associate at a Fox Chase lab.

To arrive at their findings, researchers led by Carlini analyzed DNA in blood samples drawn during a multi-site clinical trial to test an investigational combination chemotherapy regimen for metastatic colorectal cancer. The patients received intravenous irinotecan, a common drug for the disease, and capecitabine during a three-week treatment cycle.

The researchers looked at the UDP-glucuronosyltransferases gene family, which is believed to be involved in metabolizing irinotecan. Presenting her team’s findings at the 40th Annual Meeting of the American Society of Clinical Oncology meeting in New Orleans last week, Carlini said her research “indicates that patients [with] specific UGT1A7 or UGT1A9 genotypes will get more anti-tumor response from the chemotherapy combination.” She added that the patients with these mutations experience fewer side effects from the regimen.

“In reality, physicians will soon be able to personalize cancer therapies based on the tumor’s characteristics and the genetic profile of the person,” Carlini said in a statement before her presentation. “The ultimate goal is to tailor treatment that offers the most anti-tumor activity with the fewest side effects.”


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