Genetic variation in ovarian cancer thwarts treatment

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Women with a variant of the KRAS oncogene are three times more resistant to platinum chemotherapy, the standard treatment for ovarian cancer, than are women without this variant, which is found in up to 25% of new diagnoses of ovarian cancer. Testing for this biomarker, referred to simply as the KRAS variant, may help providers identify women at highest risk for poor outcomes.

As Joanne B. Weidhaas, a therapeutic radiologist at Yale University in New Haven, Connecticut, and colleagues described in the journal Oncogene, they genotyped women with epithelial ovarian cancer (EOC) for the KRAS variant and analyzed 536 of the patients for outcome, 125 for response to neoadjuvant chemotherapy, and 306 for platinum resistance. Outcomes for 79 women who also had known BRCA mutations were analyzed separately.

The investigators learned that postmenopausal EOC patients with the KRAS variant were significantly more likely to die of ovarian cancer (hazard ratio 1.67), probably because they were three times more likely to be platinum-resistant (odds ratio 3.18) than those without this variant. Blocking the variant led to a significant reduction in EOC cell growth and survival in vitro.

According to Weidhaas's team, the findings confirm the importance of the KRAS variant in EOC, and indicate that the variant is a biomarker of poor outcome in the disease likely due to platinum resistance. Direct targeting of these variants may be a viable future treatment approach.

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