New Predictive Biomarker of Survival for Surgical Metastasectomy in Colorectal Cancer

Combination treatment prior to surgery changes the clinical significance of growth factors as potential biomarkers.

Scientists have identified a new biomarker that better predicts survival following surgical resection of metastases in patients with colorectal cancer, and the change in clinical significance of the biomarker following chemotherapy.

Vascular endothelial growth factor (VEGF-A) is formed when there is a lack of oxygen in cancer cells to promote the formation of new blood vessels. The monoclonal antibody bevacizumab is designed to block VEGF-A, and inhibit vascular growth in metastasized colorectal cancer.

Previously, it was believed that VEGF-A is regulated in the metastases in the liver in the same way as in the primary tumor, and an upregulation is associated with poorer prognosis.

However, a study published in Molecular Cancer Therapeutics showed how upregulation of the growth factor VEGF-B in the primary tumor in the bowel prior to treatment was associated with poor prognosis. Meanwhile, upregulation of VEGF-B in the liver metastases after treatment was associated with a better prognosis.

“For the first time, we were able to demonstrate, in surgically resected metastases, that treatment with bevacizumab in combination with chemotherapy before metastasectomy also changes the clinical significance of the growth factors as potential biomarkers,” said lead investigator Stefan Stremitzer. “In the event of effective blockade of VEGF-A by bevacizumab, VEGF-B could be upregulated by the metastases as an alternative growth factor and could therefore serve as a new biomarker for efficacy of the treatment.”

As part of a multi-modal treatment concept, approximately 25% to 30% of patients can be cured by surgical metastasectomy. New biomarkers could increase this percentage.

“Since VEGF-A and its blockade with bevacizumab also play a major role in other cancers, such as ovarian cancer and breast cancer, VEGF-B could also serve as a new predictive biomarker and a target for new drugs for these cancers as well,” Stremitzer said. “It might be that chemotherapy could also change the clinical significance of other biomarkers.”