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Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer
Mitsukuni Suenaga1,2,3, W U Zhang4, Tetsuo Mashima5
1Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A.; m.suenaga1972@gmail.com.
Background:
Genetic variants in the CCL5/CCR5 pathway have been shown to predict regorafenib efficacy in patients with metastatic colorectal cancer (mCRC). This study investigated the biological role of CCL4 and CCL3 gene polymorphisms in patients with refractory mCRC treated using regorafenib.
Patients And Methods:
We analyzed the genomic DNA extracted from mCRC patients receiving regorafenib. Serum factor levels at baseline, day 21, and progressive disease (PD) were measured using ELISA.
Results:
Decreased CCL4 levels at day 21 or increased CCL3 levels at PD were associated with better clinical outcomes. In patients with any CCL5 rs2280789 G allele, CCL3 significantly increased between BL and day 21 compared with the A/A variant (72.7% vs. 23.1%, p=0.006), but CCL4 decreased (31.8% vs. 69.2%, p=0.043).
Conclusion:
Increased CCL3 and decreased CCL4 seen in specific genotypes may serve as potential biomarkers of regorafenib in mCRC patients.
Insights
Investigating CCL4 and CCL3 gene polymorphisms in metastatic colorectal cancer (mCRC) patients treated with regorafenib revealed potential biomarkers. Specific changes in CCL3 and CCL4 levels correlate with improved clinical outcomes, aiding treatment prediction.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- The CCL5/CCR5 pathway is implicated in predicting regorafenib efficacy for metastatic colorectal cancer (mCRC).
- This study focuses on the role of CCL4 and CCL3 gene polymorphisms in refractory mCRC patients undergoing regorafenib treatment.
Purpose of the Study:
- To investigate the biological role of CCL4 and CCL3 gene polymorphisms in patients with refractory mCRC treated with regorafenib.
- To identify potential biomarkers for regorafenib efficacy in mCRC.
Main Methods:
- Genomic DNA was analyzed from mCRC patients receiving regorafenib.
- Serum factor levels (CCL4, CCL3) were measured at baseline, day 21, and progressive disease (PD) using ELISA.
- Association between gene polymorphisms, serum levels, and clinical outcomes was assessed.
Main Results:
- Decreased CCL4 levels at day 21 or increased CCL3 levels at PD were linked to better clinical outcomes.
- Patients with the CCL5 rs2280789 G allele showed a significant increase in CCL3 and decrease in CCL4 between baseline and day 21 compared to the A/A variant.
- p-values of 0.006 for CCL3 and 0.043 for CCL4 indicate statistical significance.
Conclusions:
- Elevated CCL3 and reduced CCL4 levels, particularly in specific genotypes, may serve as predictive biomarkers for regorafenib treatment in mCRC patients.
- These findings contribute to understanding the pharmacogenomics of regorafenib in colorectal cancer.
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