French researchers cast doubt on chemo biomarker's viability

Researchers had high hopes the ERCC1 protein could be used as a biomarker to gauge the response non-small cell lung cancer patients might display to a certain kind of chemotherapy, but a group of French researchers has cast doubts on its viability.

The team, from the Institut Gustave-Roussy in Villejuif, France, couldn't replicate early results in a new study using ERCC1--a DNA repair protein--to predict how well patients with non-small-cell lung cancer would respond to cisplatin-based chemotherapy treatment. Their work is detailed in the New England Journal of Medicine, and funded, in part, by grants from Eli Lilly ($LLY) and Sanofi-Aventis. The Oncology Report summarizes the findings.

Their study--known as the Lung Adjuvant Cisplatin Evaluation Biology Biomarker (LACE) project, involved, in part, the use of 494 whole tissue tumor samples from two separate trials. They had hoped to confirm earlier work concluding that patients with tumors without the ERCC1 protein could respond favorably to cisplatin-related chemotherapy. However, as the article explains, the research team's new evaluation came to an opposite conclusion, suggesting that having ERCC1 gave patients who undertook cisplatin chemotherapy at least a small advantage. They used the 8F1 mouse monoclonal antibody to spot ERCC1 expression in tumors.

For now, they're left, in part, to speculate as to why they couldn't reproduce promising results generated in 2006 from the biology substudy of the International Adjuvant Lung Cancer Trial. The story notes that a number of factors could be involved, including the lack of proper tools to detect ERCC1 levels. Or maybe ERCC1 is just too complex in its expression to be accurately measured. More research is needed before there are answers. But that uncertainty alone, the researchers conclude, takes ERCC1 off the "reliable biomarker" list, at least for now.

- read The Oncology Report story
- here's the NEJM abstract