CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel: A systematic review

Angel T. Alvarado, Mario Bolarte-Arteaga, Mario Pineda-Pérez, César Li-Amenero, Haydee Chávez, María R. Bendezú, Jorge A. García, Juan J. Palomino-Jhong, Carmela Ferreyra-Paredes, Elizabeth J. Melgar-Merino, Doris Laos-Anchante, Pompeyo A. Cuba-Garcia, Patricia Castillo-Romero, Paulina Eliades Yarasca-Carlos, José Santiago Almeida-Galindo, Berta Loja-Herrera, Ricardo Pariona-Llanos

Research output: Contribution to journalReview articlepeer-review

Abstract

Context: Cancer is a global health problem with a growing incidence year after year, and it is projected that by 2040, there will be more than 2.4 million cases in Latin America and the Caribbean, being the second cause of death in these countries. The variability of serum levels, efficacy and safety of paclitaxel and docetaxel have been associated with allelic variants of transporter and metabolizing proteins. Aims: To review the most updated and available scientific evidence on allelic variants of CYP3A4*20, CYP3A4*22, CYP2C8*3, and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel. Methods: PRISMA was used, and a standardized search was followed in Medline/PubMed and Google Scholar with the terms: CYP3A4, CYP2C8, SLCO1B1, genetic biomarker of neuropathy and neuropathy due to paclitaxel and docetaxel. Data extraction was performed using Excel, and relevant information on allelic variants was collected as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel. Results: Eight studies indicate an association between the allelic variants of the study with peripheral neuropathy: CYP2C8*3 (HR: 1.93; 95% CI: 1.05-3.55; p=0.006), CYP3A4*22 (p=0.043), CYP3A4*20, CYP3A4*8 and CYP3A4*27 (p=5.9 × 10-5), CYP2C8 and CYP3A4 (p=1.8 × 10-6), SLCO1B1 (HR: 0.67; 95% CI: 0.46-0.97; p=0.02), SLCO1B3 (OR: 9.44), CYP3A4 (OR: 2.259; 95% CI: 1.033-4.941; p=0.038), CYP3A4*22 (RR: 6.92; 95% CI: 0.47-99.8; p=0.0766) and CYP2C8*3/*4 (RR: 1.28; 95% CI: 0.96-1.67; p=0.0898). No pharmacogenetic studies were found in cancer patients in Peruvian populations. Conclusions: Based on the review of the published scientific evidence, it is concluded that the allelic variants CYP3A4*22, CYP3A4*20 and CYP2C8*3 are associated with a modest risk of peripheral neuropathy induced by paclitaxel and docetaxel, while SLCO1B1 has less evidence.

Translated title of the contributionCYP3A4*20, CYP3A4*22, CYP2C8*3 y SLCO1B1 como biomarcadores genéticos para predecir neuropatía periférica inducida por paclitaxel y docetaxel: Una revisión sistemática
Original languageEnglish
Pages (from-to)955-967
Number of pages13
JournalJournal of Pharmacy and Pharmacognosy Research
Volume13
Issue number3
DOIs
StatePublished - May 2025

Keywords

  • CYP2C8
  • CYP3A4
  • neuropathy
  • paclitaxel
  • SLCO1B1

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