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Dilemma in metastatic colorectal cancer: VEGF versus EGRF targeting
Abstract:
The modern approach for metastatic colorectal cancer (mCRC) patients is based on the identification of oncogenic pathways, which could be targeted by specific molecules. Vascular endothelial growth factor (VEGF)- and epithelial growth factor receptor (EGFR)-related pathways represent the most important biological mechanisms for cancer development and progression. However, the most significant results by VEGF and EGFR targeting could be achieved through the combination of these drugs with standard chemotherapeutic regimens. These strategies aim to improve the resectability of liver and lung metastases. For those patients who cannot be eligible for metastases resection, a 'continuum of care' has been proposed as the best option. This strategy includes the sequential delivery of various regimens with different targeted drugs. For this reason the choice of the pathway to target, that is, VEGF or EGFR, is not a real dilemma since both these molecules would be targeted during the mCRC natural history. To date, a selection by KRAS mutational status is mandatory to identify those patients with higher probability of benefit from anti-EGFR monoclonal antibodies. In this case VEGF targeting is the only way to choose. New molecules are under evaluation to widen these treatment options.
Insights
Targeting vascular endothelial growth factor (VEGF) and epithelial growth factor receptor (EGFR) pathways improves outcomes for metastatic colorectal cancer (mCRC). Combining targeted therapies with chemotherapy offers the best strategy for managing mCRC progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Metastatic colorectal cancer (mCRC) treatment increasingly relies on targeting specific oncogenic pathways.
- Vascular endothelial growth factor (VEGF) and epithelial growth factor receptor (EGFR) pathways are critical drivers of CRC development and progression.
- Combination therapies involving VEGF and EGFR inhibitors with standard chemotherapy show significant promise.
Discussion:
- Targeted therapies aim to enhance the resectability of liver and lung metastases in mCRC patients.
- For unresectable metastases, a 'continuum of care' approach involving sequential targeted drug regimens is recommended.
- The choice between targeting VEGF or EGFR is often complementary, as both pathways may be targeted throughout the mCRC disease course.
Key Insights:
- KRAS mutational status is essential for identifying mCRC patients likely to benefit from anti-EGFR therapies.
- In KRAS-mutated cases, VEGF targeting becomes the primary therapeutic strategy.
- Ongoing research is focused on developing novel molecules to expand treatment options for mCRC.
Outlook:
- Future mCRC management will likely involve sophisticated pathway targeting and personalized treatment sequencing.
- Continued investigation into new targeted agents is crucial for improving patient survival and quality of life.
- Integration of biomarker-driven selection (e.g., KRAS status) will refine therapeutic strategies.
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