ERCC2 validated as chemotherapy response biomarker in bladder cancer

By Shreeya Nanda

Somatic mutations in the helicase-encoding ERCC2 gene are associated with response to neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive urothelial bladder carcinoma.

Among 48 patients who received three cycles of chemotherapy in two clinical trials of neoadjuvant cisplatin-based treatment, 10 had tumours with nonsynonymous mutations in ERCC2.

ERCC2 mutations were significantly associated with response, such that 40% of 20 responders harboured a mutation compared with only 7% of 28 nonresponders, a significant difference. Moreover, overall survival was significantly longer for participants with versus without an ERCC2 alteration.

These findings replicate those of a discovery cohort that showed an association between ERCC2 mutations and pathological response, say Jonathan Rosenberg (Memorial Sloan Kettering Cancer Center, New York, USA) and co-authors in JAMA Oncology.

But they add that as a biomarker ERCC2 has limitations - it is not 100% specific and mutations are found in less than half of responders, suggesting that other factors are involved.

The team concludes: "Further characterization of specific ERCC2 mutations to improve specificity and development of a more sensitive integrated panel of DNA repair biomarkers may inform clinical decision-making."

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