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Clues to Successful Chemotherapy

Genetic testing not only opens a window into one’s personal cancer horizon, it may also unlock a medical hope chest. Researchers like USC’s Heinz-Josef Lenz are genetic detectives in search of clues that could lead oncologists to better, less toxic chemotherapy customized for each patient. New research from Lenz’s lab shows, for example, that variations in a key gene – called XPD – are linked to a better response to platinum-based anti-cancer drugs among colon cancer patients.


A simple blood test before chemotherapy can steer patients toward more effective drugs to combat their cancer.
Xeroderma pigmentosum group D, or XPD, is a protein made by the body that’s critical to repairing damaged DNA. The more efficiently someone’s body fixes its broken DNA, unfortunately, the more a cancerous tumor will resist platinum-based chemotherapy drugs (such as oxaliplatin). But not all XPD genes are created equal. Certain small bits of the gene – or polymorphisms – exist in different forms in the human population. Lenz and Keck School resident David J. Park tested 70 patients with advanced metastatic colorectal cancer for specific polymorphisms in the XPD gene, and administered chemotherapy consisting of 5-FU (fluorouracil) and oxaliplatin to the patients.

Twenty-four percent of patients with one variety of one polymorphism responded to the drugs, meaning tumors shrank by 50 percent or more for at least six weeks. In each of the other two patient groups with different polymorphisms, only 10 percent of patients responded.

The important polymorphism is called Lys751Gln. Patients with tumors that responded best to treatment had a genotype called Lys/Lys, while those whose tumors responded the least had a genotype called Gln/Gln.

Lenz’s group already has shown that several other DNA repair genes, such as ERCC1 and XRCC1, seem to predict how well certain chemotherapy drugs will combat colorectal and other cancers. The group continues to study just how variations in the XPD gene affect DNA repair and other factors important in drug resistance.

– Alicia Di Rado



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