Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients.

Suenaga, Mitsukuni; Zhang, W U; Mashima, Tetsuo; Schirripa, Marta; Cao, Shu; Okazaki, Satoshi; Berger, Martin D.; Miyamoto, Yuji; Barzi, Afsaneh; Yamaguchi, Toshiharu; Lenz, Heinz-Josef (2021). Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients. Cancer genomics & proteomics, 18(3), pp. 317-324. International Institute of Anticancer Research 10.21873/cgp.20262

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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.

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