Influence of genetic polymorphisms in vascular endothelial-related genes on the clinical outcome of axitinib in patients with metastatic renal cell carcinoma
| Title: | Influence of genetic polymorphisms in vascular endothelial-related genes on the clinical outcome of axitinib in patients with metastatic renal cell carcinoma |
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| Authors: | Kazuyuki Numakura, Ryoma Igarashi, Makoto Takahashi, Taketoshi Nara, Sohei Kanda, Mitsuru Saito, Shintaro Narita, Takamitsu Inoue, Takenori Niioka, Masatomo Miura, Tomonori Habuchi |
| Source: | Cancer Biology & Therapy, Vol 25, Iss 1 (2024) |
| Publisher Information: | Taylor & Francis Group, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | Renal cell carcinoma, axitinib, polymorphisms, ACE, NOS3, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Objective Axitinib is an oral multi-target tyrosine kinase inhibitor used for the treatment of renal cell carcinoma (RCC). Because of the severe adverse events (AEs) associated with axitinib, patients often need dose reductions or discontinue its use, highlighting the need for effective biomarkers to assess efficacy and/or AEs. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in the pharmacodynamic action of axitinib and clinical prognosis and AEs in metastatic RCC (mRCC) patients.Methods This study included 80 mRCC patients treated with first-, second-, or third-line axitinib (5 mg orally twice daily). Clinical parameters and genetic polymorphisms were examined in 75 cases (53 males and 22 females). We assessed three SNPs in each of three candidate genes namely, angiotensin-converting enzyme (ACE), nitric oxide synthase 3 (NOS3), and angiotensin II receptor type 1 (AT1R), all of which are involved in axitinib effects on vascular endothelial function.Results Axitinib-treated patients carrying the ACE deletion allele suffered more frequently from hand-foot syndrome and a deterioration in kidney function (p = .045 and p = 0.005, respectively) whereas those carrying the NOS3 G allele suffered more frequently from proteinuria and multiple AEs (p = .025 and p = 0.036, respectively).Conclusions Our study found that the ACE deletion allele and the NOS3 G allele are associated with increased AEs. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 15384047 1555-8576 1538-4047 |
| Relation: | https://doaj.org/toc/1538-4047; https://doaj.org/toc/1555-8576 |
| DOI: | 10.1080/15384047.2024.2312602 |
| Access URL: | https://doaj.org/article/4e0e873027ee447c846d4cb65a173c69 |
| Accession Number: | edsdoj.4e0e873027ee447c846d4cb65a173c69 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15384047 15558576 |
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| DOI: | 10.1080/15384047.2024.2312602 |
| Published in: | Cancer Biology & Therapy |
| Language: | English |