Novel markers that predict the success of colorectal cancer drug therapy

This study evaluated whether microRNA expression was predictive of treatment success in patients with metastatic colorectal cancer (late stage cancer that has spread to distant sites).

MicroRNA’s are small messengers that help to regulate expression of genes. Recent studies have shown that dysregulation of certain microRNAs is associated with the beginning of colorectal cancer. In addition, altered levels of microRNAs may reduce a patients’ sensitivity to a number of anti-cancer therapies.

Both cetuximab (Erbitux) and panitumumab (Vectibix) are new drugs that bind to the epidermal growth factor receptor (EGFR) protein, blocking their effects. As EGFR is involved in cancer growth and spread, they can help slow the cancer. However, these drugs are not effective for all patients and it would be useful to find markers that can predict if they will be useful or not. Specific microRNAs might be useful predictors of the efficacy of cetuximab and panitumumab.

A total of 183 patients with metastatic colorectal cancer were included in the study. Patients were evaluated from two separate studies: study 1 included 74 patients and study 2 included 109 patients. Patients were treated with cetuximab or panitumumab alone (19 patients), or in combination with chemotherapy (164 patients). Their tumor samples were screened for microRNA expression (presence). Overall survival (time until death from any cause) and progression free survival (time following treatment before the disease progresses) were also recorded.

One cluster of microRNAs (Let-7c/miR-99a/miR-125b) were associated with patient outcome in both study groups. In study 1 patients with high levels of these microRNAs had a longer progression free survival. It took an average of 6.1 months for the disease to progress compared to only 2.3 months in patients with low levels. In study 2 it took an average of 7.8 months for the cancer to progress in patients with high levels of these microRNAs compared to 4.3 months for patients with low levels.

In study 1 overall survival was also prolonged in patients with high levels of Let-7c/miR-99a/miR-125b, an average survival of 29.8 months compared to 7 months for patients with low expression. This prolonged survival time was also seen in study 2, 12.8 month average survival time for patients with high levels compared to 7.5 months for patients with low expression.

The authors concluded that analysis of the microRNA cluster Let-7c/miR-99a/miR-125b could be useful for predicting which patients will respond to cetuximab and panitumumab.

This is a relatively early study and further research is required to fully understand the role of this microRNA cluster.