Amira B. Kassem, Amira Abdelmonem Ahmed, Noha A. El‑Bassiouny, Gamal Omran, Mahmoud Mohamed Kamel, Ahmed El Bastawisy, Nermeen Nabeel Abuelsoud
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Blood samples were collected, and SOD2 and EPHA5 gene polymorphisms were detected using real-time PCR. All patients were assessed using the Common Terminology Criteria for Adverse Events v 5.0 score, and the biomarker was measured from serum using an enzyme immunosorbent assay at baseline and three months after taxanes treatment.</p><h3>Results</h3><p>The detected SOD2 (rs4880) genetic polymorphisms were AA (39%), AG (49%), GG (12%), CC (49%), TC (42%), and TT (9%) in EPHA5 (rs7349683). A statistically significant difference existed between EPHA5 C > T genotypes regarding the NFL levels and delta NFL (<i>p</i> value = 0.000 and 0.010<b>,</b> respectively). Also, there was a significant association between different EPHA5 C > T genotypes and neurotoxicity grades post-taxanes treatment (<i>p</i> value = 0.010). There was a statistically significant difference in fatigue associated with the EPHA5 gene (<i>p</i> value = 0.011).</p><h3>Conclusion</h3><p>Detecting EPHA5 genetic polymorphisms before administering taxanes is highly recommended for assessing neurotoxicity risk. NFL measurement is recommended to be used in the early identification of taxane-induced neurotoxicity.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"11 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-025-00827-1","citationCount":"0","resultStr":"{\"title\":\"EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients\",\"authors\":\"Amira B. Kassem, Amira Abdelmonem Ahmed, Noha A. El‑Bassiouny, Gamal Omran, Mahmoud Mohamed Kamel, Ahmed El Bastawisy, Nermeen Nabeel Abuelsoud\",\"doi\":\"10.1186/s43094-025-00827-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Breast cancer is the leading cause of cancer-related deaths globally, with taxanes being the most commonly used chemotherapeutic agents. However, adverse effects like myelosuppression, neuropathy, and hypersensitivity reactions exist.</p><h3>Objective</h3><p>To find the association between genetic polymorphisms in SOD2 rs4880 and EPHA5 rs7349683 and taxane-induced neurotoxicity, also to prospectively evaluate the usefulness of serum neurofilament light chain (sNFL) levels as an early biomarker of development neurotoxicity in different genotypes.</p><h3>Methods</h3><p>One hundred breast cancer patients prospectively received taxane treatment. Blood samples were collected, and SOD2 and EPHA5 gene polymorphisms were detected using real-time PCR. All patients were assessed using the Common Terminology Criteria for Adverse Events v 5.0 score, and the biomarker was measured from serum using an enzyme immunosorbent assay at baseline and three months after taxanes treatment.</p><h3>Results</h3><p>The detected SOD2 (rs4880) genetic polymorphisms were AA (39%), AG (49%), GG (12%), CC (49%), TC (42%), and TT (9%) in EPHA5 (rs7349683). A statistically significant difference existed between EPHA5 C > T genotypes regarding the NFL levels and delta NFL (<i>p</i> value = 0.000 and 0.010<b>,</b> respectively). Also, there was a significant association between different EPHA5 C > T genotypes and neurotoxicity grades post-taxanes treatment (<i>p</i> value = 0.010). There was a statistically significant difference in fatigue associated with the EPHA5 gene (<i>p</i> value = 0.011).</p><h3>Conclusion</h3><p>Detecting EPHA5 genetic polymorphisms before administering taxanes is highly recommended for assessing neurotoxicity risk. 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EPHA5 and SOD2 genetic variants and their link to neurofilament light chain: early detection of taxane-induced neurotoxicity in Egyptian breast cancer patients
Background
Breast cancer is the leading cause of cancer-related deaths globally, with taxanes being the most commonly used chemotherapeutic agents. However, adverse effects like myelosuppression, neuropathy, and hypersensitivity reactions exist.
Objective
To find the association between genetic polymorphisms in SOD2 rs4880 and EPHA5 rs7349683 and taxane-induced neurotoxicity, also to prospectively evaluate the usefulness of serum neurofilament light chain (sNFL) levels as an early biomarker of development neurotoxicity in different genotypes.
Methods
One hundred breast cancer patients prospectively received taxane treatment. Blood samples were collected, and SOD2 and EPHA5 gene polymorphisms were detected using real-time PCR. All patients were assessed using the Common Terminology Criteria for Adverse Events v 5.0 score, and the biomarker was measured from serum using an enzyme immunosorbent assay at baseline and three months after taxanes treatment.
Results
The detected SOD2 (rs4880) genetic polymorphisms were AA (39%), AG (49%), GG (12%), CC (49%), TC (42%), and TT (9%) in EPHA5 (rs7349683). A statistically significant difference existed between EPHA5 C > T genotypes regarding the NFL levels and delta NFL (p value = 0.000 and 0.010, respectively). Also, there was a significant association between different EPHA5 C > T genotypes and neurotoxicity grades post-taxanes treatment (p value = 0.010). There was a statistically significant difference in fatigue associated with the EPHA5 gene (p value = 0.011).
Conclusion
Detecting EPHA5 genetic polymorphisms before administering taxanes is highly recommended for assessing neurotoxicity risk. NFL measurement is recommended to be used in the early identification of taxane-induced neurotoxicity.
期刊介绍：
Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
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