Can protein levels predict the response to bevacizumab in colorectal cancer?

This study investigated whether the levels of certain proteins could be used to predict response to treatment with bevacizumab or chemotherapy in patients with colorectal cancer which has spread beyond the original tumor site. Three proteins were identified as potential biomarkers.

In as much as 50% of patients diagnosed with colorectal cancer (CRC), the cancer has already metastasized (spread from the original tumor site). Treatments such as chemotherapy and drugs including bevacizumab (Avastin, a treatment that blocks the production of new blood vessels that tumors need for growth) have improved survival outcomes.

Biomarkers are naturally occurring body substances or measurements that are associated with a disease and are often used for predicting the progression or outcome of a disease. Some potential biomarkers to predict the response to bevacizumab have been discovered but none have been validated. The identification of biomarkers is important as they can help to determine the most beneficial treatment, and avoid treating patients who are unlikely to respond.

This study aimed to determine whether the levels of certain proteins could be used to predict response to treatment with bevacizumab and chemotherapy in patients with metastatic CRC. 23 patients took part. Protein levels were measured before patients underwent treatment with bevacizumab and chemotherapy. Patients who had a progression-free survival (PFS, time from treatment until disease progression) of 9 months or more were determined to be responders to the treatment. Patients with shorter PFS were referred to as non-responders. 

3 proteins (APOE, AGT and DBP) associated with survival outcomes were identified. Patients with higher APOE levels in the blood were 17% more likely to have a shorter PFS and overall survival (OS, time from treatment until death from any cause). Patients with higher AGT blood levels were 12% more likely to have a shorter OS. 

Higher levels of APOE in the stroma (connective tissue of an organ) increased the risk of a shorter PFS by 34% and OS by 22%. Higher levels of  APOE in the epithelium (the lining of an organ), however, increased the likelihood of a longer PFS and OS.

Higher DBP levels in the stroma increased the risk of a shorter OS by 22%. Higher levels of AGT in the epithelium increased the likelihood of a longer PFS by 10%. 

The authors concluded that APOE, AGT and DPB are expressed at different levels in different cells and are associated with the patient’s response to bevacizumab and chemotherapy. They suggest that a set of biomarkers, rather than a single biomarker, could be useful in predicting survival outcomes in metastatic CRC patients.

This trial included a small number of patients. These findings need to be confirmed by larger scale studies. 

Consult your doctor if you are concerned about the likelihood that you will respond to your treatment.