ArticleCancer chemotherapy and pharmacology2024
Association of VEGFA and CCL4L2 polymorphisms with hand-foot skin reaction and survival of regorafenib in Japanese patients with colorectal cancer.
Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Association of IL12RB2, RORC, and class II HLA polymorphisms with severe erythema multiforme of regorafenib in Japanese patients with colorectal cancer.Cancer chemotherapy and pharmacology · 2025Article
- CCL4L2 participates in tendinopathy progression by promoting macrophage inflammatory responses: a single-cell analysis.Journal of orthopaedic surgery and research · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTreatment with regorafenib, which inhibits vascular endothelial growth factor (VEGF) receptor, frequently results in hand-foot skin reaction (HFSR), requiring treatment discontinuation or dose reduction. In our prospective study of regorafenib on patients with metastatic colorectal cancer, 17% of patients developed grade 3 HFSR. Herein, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe HFSR.
methodsTo identify associated polymorphisms, exploratory whole-exome sequencing focusing on factors related to VEGF-mediated signaling pathways was first performed in seven patients each, with grade 3 HFSR and without HFSR. The identified HFSR-associated polymorphisms were analyzed in all the 40 patients.
resultsThe genotype frequency of rs3025009 G/A or A/A in the gene encoding VEGF-A (VEGFA) in patients with ≥ grade 2 HFSR was significantly higher than in other patients (P = 0.0257, Pc = 0.0771 [Bonferroni correction]). The frequency of C-C motif of chemokine ligand 4-like 2 (CCL4L2) rs3744596 A/T or T/T in patients with grade 3 HFSR was significantly lower than in others (P = 0.00894, Pc = 0.0268). The combination of the risk genotypes VEGFA rs3025009 G/A or A/A and CCL4L2 rs3744596 A/A was significantly associated with a higher incidence of grade 3 (P = 0.000614, Pc = 0.00246) and a longer median progression-free survival (P = 0.0234) than others.
conclusionsThese VEGF-related polymorphisms were found to be associated with HFSR and the survival benefits of regorafenib treatment. TRIAL REGISTRATION NUMBER AND DATE: UMIN000013939, registered on May 12, 2014, when 6 months after the approval by the Institutional Review Board of Showa University.
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