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Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer
Satoshi Otsu1, Shuichi Hironaka2
1Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1, Idaigaoka, Hasama-machi, Yufu City 879-5593, Oita, Japan.
Abstract:
Colorectal cancer is the third most common disease and the second most common cause of death around the world. The drug for second-line treatment depends on the drugs used in first-line treatment and the biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on the biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers have been established for the selection of angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of the therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be promising biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.
Insights
Colorectal cancer treatment relies on biomarkers. This study explores selecting among three angiogenesis inhibitors (bevacizumab, ramucirumab, aflibercept) for second-line therapy, highlighting potential VEGF biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colorectal cancer is a leading cause of death globally.
- Second-line treatment selection depends on prior therapies and biomarkers like RAS, BRAF, dMMR/MSI-H, TMB-H, and HER2.
- Angiogenesis inhibitors are frequently used in second-line colorectal cancer treatment.
Purpose of the Study:
- To clarify the rationale for selecting among bevacizumab, ramucirumab, and aflibercept in second-line colorectal cancer treatment.
- To investigate potential biomarkers for predicting the efficacy of these angiogenesis inhibitors.
Main Methods:
- Review of established biomarkers for first-line colorectal cancer treatment.
- Analysis of clinical practice regarding second-line treatment with angiogenesis inhibitors.
- Exploration of previous biomarker studies suggesting VEGF-A and VEGF-D as potential predictors for angiogenesis inhibitor efficacy.
Main Results:
- Three angiogenesis inhibitors (bevacizumab, ramucirumab, aflibercept) are available for second-line colorectal cancer treatment, each with distinct mechanisms.
- No definitive biomarkers are currently established for selecting among these inhibitors.
- Angiogenesis-related factors, such as VEGF-A and VEGF-D measured in plasma, show promise as predictive biomarkers.
Conclusions:
- There is a need to clarify the selection rationale for angiogenesis inhibitors in second-line colorectal cancer therapy.
- VEGF-A and VEGF-D represent promising biomarkers for predicting therapeutic efficacy.
- Further research into biomarker-guided selection can optimize patient outcomes.
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