Markers of Response to Antiangiogenic Therapies in Colorectal Cancer: Where are We Now and What should be Next?

Abstract

Despite advances in the treatment of colorectal cancer (CRC), it remains the second most common cause of cancer-related death in the Western world. Angiogenesis is a complex process that involves the formation of new blood vessels from preexisting vessels. It is essential for promoting cancer survival, growth, and dissemination. The inhibition of angiogenesis has been shown to prevent tumor progression experimentally, and several chemotherapeutic targets of tumor angiogenesis have been identified. These include anti-vascular endothelial growth factor (VEGF) treatments, such as bevacizumab (a VEGF-specific binding antibody) and anti-VEGF receptor tyrosine kinase inhibitors, although antiangiogenic therapy has been shown to be effective in the treatment of several cancers, including CRC. However, it is also associated with its own side effects and financial costs. Therefore, the identification of biomarkers that are able to identify patients who are more likely to benefit from antiangiogenic treatment is very important. This article intends to be a concise summary of the potential biomarkers that can predict or prognosticate the benefit of antiangiogenic treatments in CRC, and also what we can expect in the near future.

Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab

“…VEGF is the most widely studied biomarker for predicting response to antiangiogenic treatment 21, 22 . An association between the efficacy of antiangiogenic treatments and VEGF tumor levels has been reported in several studies, with contrasting results 19, 23, 24 .…”

Phase 1 trial of ontuxizumab (MORAb‐004) in children with relapsed or refractory solid tumors: A report from the Children's Oncology Group Phase 1 Pilot Consortium (ADVL1213)

“…17,18 Elevated levels of soluble PDGFRβ in CSF have been found to correlate with brain pericyte injury, suggesting that soluble pericyte cell surface proteins, such as endosialin and PDGFRβ, may be potential biomarkers for ontuxizumab activity. 15,19 Biomarker evaluation demonstrated that circulating endosialin and PDGFRβ in plasma were highly variable.…”

“…Prior studies have demonstrated a potential role for circulating soluble cell surface proteins such as vascular endothelial growth factor receptor in the systemic circulation as biomarkers for pharmacologic and clinical activity of antiangiogenic therapy. 17,18 Elevated levels of soluble PDGFR in CSF have been found to correlate with brain pericyte injury, suggesting that soluble pericyte cell surface proteins, such as endosialin and PDGFR , may be potential biomarkers for ontuxizumab activity. 15,19 Biomarker evaluation demonstrated that circulating endosialin and PDGFR in plasma were highly variable.…”

The role of microvessel density, lymph node metastasis, and tumor size as prognostic factors of distant metastasis in colorectal cancer

“…Tumor angiogenesis (the formation of new blood vessels) is essential for tumor growth and metastasis (2,4). The development of new blood vessels is a complex phenomenon involving growth factors, extracellular matrix enzymes, endothelial cell migration and proliferation, lumen formation, and anastomosis with other vessels (5,6).…”

“…It is the third most common malignancy and second most common cause of cancer-related death in developed countries (2). Intensive surveillance after colorectal cancer surgery improves survival because early diagnosis of recurrence increases the frequency of its curative resection (3).…”