Evolving role of gene expression signatures as biomarkers in early-stage colon cancer

Colorectal cancer (CRC) is a major health problem in the USA and worldwide. At the time of initial presentation, approximately 26 % of CRC patients will have stage II disease while another 30 % will present with stage III disease. Although surgical resection plays a critical role in the management of patients who have early-stage disease, it is usually not curative by itself. As a result, adjuvant chemotherapy is generally administered to eradicate clinically occult micrometastatic disease. It is now being increasingly realized that not all patients with stage II and III disease derive significant benefit from adjuvant chemotherapy. Moreover, due to a growing concern for long-term chemotherapy-associated adverse effects, its utility in unselected stage II/III patients is now being questioned.

Significant efforts have been made in recent years to identify potential biomarkers that would help to define the subset of stage II and III colon cancer patients expected to derive significant benefit from adjuvant chemotherapy, especially in those with borderline indications. Oncotype DX Colon Cancer Assay and ColoPrint are gene expression profiling-based recurrence score (RS) assays that have been developed with this intent. The greatest utility of RS assay has been conventionally believed to be for identifying recurrence risk in stage II patients. Recent data now suggests that stage III patients similar to stage II patients, vary in their tumor recurrence risk and that there might be a role for a more selective approach in treating these patients, based on the results of RS assays.

In such an evolving landscape, this article aims to review the current role of gene expression signatures such as Oncotype DX and ColoPrint in the management of early-stage colon cancer.