ArticleClinical colorectal cancer2018
Gene Polymorphisms in the CCL5/CCR5 Pathway as a Genetic Biomarker for Outcome and Hand-Foot Skin Reaction in Metastatic Colorectal Cancer Patients Treated With Regorafenib.
Article in Clinical colorectal cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- CCL5 improves radiation resistance through activation of the AMPK/mTOR pathway in adenoid cystic carcinoma.Journal of translational medicine · 2026Article
- Article
- Prognostic impact of hand-foot skin reaction in regorafenib-treated adult-type diffuse gliomas: A multicenter Turkish Oncology Group study.Scientific reports · 2025Article
- Article
- Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.Cancers · 2024Review
- Association of VEGFA and CCL4L2 polymorphisms with hand-foot skin reaction and survival of regorafenib in Japanese patients with colorectal cancer.Cancer chemotherapy and pharmacology · 2024Article
- Article
- The regulatory network of the chemokine CCL5 in colorectal cancer.Annals of medicine · 2023Review
- Article
- Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC.Pharmaceutics · 2022Review
- A promising research direction for colorectal cancer immunotherapy: The regulatory mechanism of CCL5 in colorectal cancer.Frontiers in oncology · 2022Review
- Review
- Efficacy and Safety of Regorafenib Monotherapy among Patients with Previously Treated Metastatic Colorectal Cancer in a Chinese Population: A Real-World Exploratory Study.International journal of general medicine · 2021Article
- Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment.International journal of general medicine · 2021Article
- Clinical and molecular distinctions in patients with refractory colon cancer who benefit from regorafenib treatment.Therapeutic advances in medical oncology · 2020Article
- Molecular insight of regorafenib treatment for colorectal cancer.Cancer treatment reviews · 2019Review
- Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma.World journal of gastroenterology · 2019Review
- Genetic variants in CCL5 and CCR5 genes and serum VEGF-A levels predict efficacy of bevacizumab in metastatic colorectal cancer patients.International journal of cancer · 2019Article
- Review
- Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients.Cancer genomics & proteomicsArticle
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Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe C-C motif chemokine ligand 5/C-C motif chemokine receptor 5 (CCL5/CCR5) pathway has been shown to induce endothelial progenitor cell migration, resulting in increased vascular endothelial growth factor A expression. We hypothesized that genetic polymorphisms in the CCL5/CCR5 pathway predict efficacy and toxicity in patients with metastatic colorectal cancer (mCRC) treated with regorafenib. PATIENTS AND
methodsWe analyzed genomic DNA extracted from 229 tumor samples from 2 different cohorts of patients who received regorafenib: an evaluation cohort of 79 Japanese patients and a validation cohort of 150 Italian patients. Single nucleotide polymorphisms of CCL5/CCR5 pathway-related genes were analyzed by PCR-based direct sequencing.
resultsCCL4 rs1634517 and CCL3 rs1130371 were associated with progression-free survival in the evaluation cohort (hazard ratio [HR] 1.54, P = .043; HR 1.48, P = .064), and progression-free survival (HR 1.74, P < .001; HR 1.66, P = .002) and overall survival (HR 1.65, P = .004; HR 1.65, P = .004) in the validation cohort. The allelic frequencies of CCL5 single nucleotide polymorphisms varied between the evaluation and validation cohorts (G/G variant in rs2280789, 21.5% vs. 1.3%, P < .001; T/T variant in rs3817655, 22.8% vs. 2.7%, P < .001). In the evaluation cohort, patients with the G/G variant in rs2280789 had a higher incidence of grade 3+ hand-foot skin reaction compared to any A allele (53% vs. 27%, P = .078), and similarly to the T/T variant in rs3817655 compared to any A allele (56% vs. 26%, P = .026).
conclusionGenetic variants in the CCL5/CCR5 pathway may serve as prognostic markers and may predict severe hand-foot skin reaction in mCRC patients receiving regorafenib therapy.
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