Targeted Monoclonal Antibody Therapy in Metastatic Colorectal Cancer

Metastatic colorectal cancer (mCRC) remains a leading cause of cancer mortality worldwide. Conventional cytotoxic chemotherapy has formed the backbone of treatment, but advances in molecular oncology have introduced targeted monoclonal antibodies (mAbs) that selectively inhibit key signalling pathways driving tumour growth and angiogenesis. Agents directed against the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have shown efficacy in patients whose tumours lack activating RAS mutations, improving progression-free and overall survival when combined with fluoropyrimidine-based chemotherapy. Similarly, inhibition of vascular endothelial growth factor (VEGF) by bevacizumab disrupts tumour neovascularisation and is widely used across multiple lines of therapy. Biomarker-guided selection—based on RAS and BRAF mutation status, tumour sidedness, and mismatch repair proficiency—has become essential to maximise benefit and limit toxicity. Despite these advances, primary and acquired resistance to mAb therapy remains a challenge, driven by compensatory pathway activation, tumour heterogeneity and microenvironmental factors. Current research focuses on novel antibody formats, bispecific constructs, enhanced drug delivery systems and combination strategies with immunotherapy or small-molecule inhibitors to overcome resistance and extend survival in diverse patient populations.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Targeted Monoclonal Antibody Therapy in Metastatic Colorectal Cancer publication trend

The graph below shows the total number of articles in targeted monoclonal antibody therapy in metastatic colorectal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Monoclonal antibody: A laboratory-engineered protein designed to bind a specific antigen, thereby blocking signalling pathways or recruiting immune cells to destroy tumour cells.

Epidermal growth factor receptor (EGFR): A cell-surface tyrosine kinase receptor whose activation promotes cell proliferation, survival and migration; overexpressed or dysregulated in many colorectal tumours.

Vascular endothelial growth factor (VEGF): A key mediator of angiogenesis that stimulates the formation of new blood vessels to supply growing tumours.

RAS wild-type: Tumours lacking activating mutations in KRAS or NRAS genes, predictive of responsiveness to EGFR-targeted monoclonal antibodies.

Progression-free survival (PFS): The length of time during and after treatment in which a patient’s disease does not worsen, commonly used as an efficacy endpoint in clinical trials.

Tumour sidedness: The anatomical origin of colorectal cancer (left vs right colon), which influences molecular profile, biology and response to targeted therapies.

References

1. Fluoropyrimidine type, patient age, tumour sidedness and mutation status as determinants of benefit in patients with metastatic colorectal cancer treated with EGFR monoclonal antibodies: individual patient data pooled analysis of randomised trials from the ARCAD database. British Journal of Cancer (2024).
2. Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer. Cells (2024).
3. Precision Medicine for Metastatic Colorectal Cancer: Where Do We Stand?. Cancers (2024).
4. Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers. Biomedicines (2021).