Regorafenib Applications in Metastatic Colorectal Cancer

Regorafenib is an oral multi-target tyrosine kinase inhibitor deployed as a salvage therapy for metastatic colorectal cancer that has progressed after standard chemotherapy and biologics. By inhibiting kinases associated with tumour angiogenesis, oncogenesis and maintenance of the tumour microenvironment, regorafenib extends overall survival modestly and offers disease stabilisation in a subset of heavily pretreated patients. Its efficacy is constrained by off-target toxicities—most notably hand-foot skin reaction, hypertension and fatigue—and by the emergence of primary and acquired resistance mechanisms. Current strategies seek to refine patient selection through biomarkers of anti-angiogenic response and to enhance therapeutic index via combination regimens and dose optimisation. Preclinical models integrating genomic, transcriptomic and functional imaging analyses have uncovered resistance pathways and potential synergistic partners, laying the foundation for novel treatment approaches and precision medicine guidance in this refractory setting.

Research from Nature Portfolio

A study investigating angiogenesis-related gene polymorphisms identified a single nucleotide polymorphism in the VEGF-A gene that correlates independently with progression-free and overall survival in patients receiving regorafenib. By integrating the VEGF-A genotype with clinical performance status, investigators stratified patients into three distinct prognostic groups, offering a potential tool for optimising candidate selection. This seminal finding highlights the prospect of genetic biomarkers to predict therapeutic benefit and guide personalised regorafenib therapy in metastatic colorectal cancer.

Regorafenib Applications in Metastatic Colorectal Cancer publication trend

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

Technical terms

Metastatic colorectal cancer (mCRC): Colorectal cancer that has spread beyond the primary site to distant organs.

Multi-target tyrosine kinase inhibitor (mTKI): A compound that blocks multiple tyrosine kinases involved in tumour growth and angiogenesis.

Angiogenesis: The process of new blood vessel formation, critical for tumour growth and metastasis.

Progression-free survival (PFS): The length of time during and after treatment in which a patient’s disease does not worsen.

Overall survival (OS): The duration from treatment initiation until death from any cause.

Xenograft model: An experimental system in which human tumour tissue is implanted into immunodeficient animals to study cancer therapies.

Single nucleotide polymorphism (SNP): A variation at a single DNA base position in the genome, which may affect individual response to therapy.

References

1. Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer. Journal of Experimental & Clinical Cancer Research (2024).
2. ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization. BMC Medicine (2023).
3. Synergistic antitumor activity of regorafenib and rosuvastatin in colorectal cancer. Frontiers in Pharmacology (2023).
4. Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients. Scientific Reports (2016).