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

doi:10.56499/jppres24.2125_13.3.955

CYP3A420, CYP3A422, 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

International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMOGEM)
Universidad San Ignacio de Loyola
Universidad Continental
Faculty of Health Sciences
Universidad Científica del Sur
Victor Larco Herrera Hospital
Faculty of Pharmacy and Biochemistry
Universidad Nacional "San Luis Gonzaga" de Ica
Universidad Nacional Mayor de San Marcos
Universidad Peruana de Ciencias Aplicadas

Research output: Contribution to journal › Review article › peer-review

2 Scopus citations

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 contribution	CYP3A420, CYP3A422, CYP2C8*3 y SLCO1B1 como biomarcadores genéticos para predecir neuropatía periférica inducida por paclitaxel y docetaxel: Una revisión sistemática
Original language	English
Pages (from-to)	955-967
Number of pages	13
Journal	Journal of Pharmacy and Pharmacognosy Research
Volume	13
Issue number	3
DOIs	https://doi.org/10.56499/jppres24.2125_13.3.955
State	Published - May 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CYP2C8
CYP3A4
SLCO1B1
neuropathy
paclitaxel

Access to Document

10.56499/jppres24.2125_13.3.955

Cite this

Alvarado, A. T., Bolarte-Arteaga, M., Pineda-Pérez, M., Li-Amenero, C., Chávez, H., Bendezú, M. R., García, J. A., Palomino-Jhong, J. J., Ferreyra-Paredes, C., Melgar-Merino, E. J., Laos-Anchante, D., Cuba-Garcia, P. A., Castillo-Romero, P., Yarasca-Carlos, P. E., Almeida-Galindo, J. S., Loja-Herrera, B., & Pariona-Llanos, R. (2025). CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel: A systematic review. Journal of Pharmacy and Pharmacognosy Research, 13(3), 955-967. https://doi.org/10.56499/jppres24.2125_13.3.955

@article{bec8cce8177f442fbec8172bb9680d00,

title = "CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel: A systematic 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 {\texttimes} 10-5), CYP2C8 and CYP3A4 (p=1.8 {\texttimes} 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.",

keywords = "CYP2C8, CYP3A4, SLCO1B1, neuropathy, paclitaxel",

author = "Alvarado, \{Angel T.\} and Mario Bolarte-Arteaga and Mario Pineda-P{\'e}rez and C{\'e}sar Li-Amenero and Haydee Ch{\'a}vez and Bendez{\'u}, \{Mar{\'i}a R.\} and Garc{\'i}a, \{Jorge A.\} and Palomino-Jhong, \{Juan J.\} and Carmela Ferreyra-Paredes and Melgar-Merino, \{Elizabeth J.\} and Doris Laos-Anchante and Cuba-Garcia, \{Pompeyo A.\} and Patricia Castillo-Romero and Yarasca-Carlos, \{Paulina Eliades\} and Almeida-Galindo, \{Jos{\'e} Santiago\} and Berta Loja-Herrera and Ricardo Pariona-Llanos",

note = "Publisher Copyright: {\textcopyright} 2025 Journal of Pharmacy \& Pharmacognosy Research.",

year = "2025",

month = may,

doi = "10.56499/jppres24.2125\_13.3.955",

language = "Ingl{\'e}s",

volume = "13",

pages = "955--967",

journal = "Journal of Pharmacy and Pharmacognosy Research",

issn = "0719-4250",

number = "3",

}

Alvarado, AT, Bolarte-Arteaga, M, Pineda-Pérez, M, Li-Amenero, C, Chávez, H , Bendezú, MR , García, JA , Palomino-Jhong, JJ, Ferreyra-Paredes, C, Melgar-Merino, EJ , Laos-Anchante, D , Cuba-Garcia, PA , Castillo-Romero, P , Yarasca-Carlos, PE , Almeida-Galindo, JS, Loja-Herrera, B & Pariona-Llanos, R 2025, 'CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel: A systematic review', Journal of Pharmacy and Pharmacognosy Research, vol. 13, no. 3, pp. 955-967. https://doi.org/10.56499/jppres24.2125_13.3.955

CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel: A systematic review. / Alvarado, Angel T.; Bolarte-Arteaga, Mario; Pineda-Pérez, Mario et al.
In: Journal of Pharmacy and Pharmacognosy Research, Vol. 13, No. 3, 05.2025, p. 955-967.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - CYP3A4*20, CYP3A4*22, CYP2C8*3 and SLCO1B1 as genetic biomarkers to predict peripheral neuropathy induced by paclitaxel and docetaxel

T2 - A systematic review

AU - Alvarado, Angel T.

AU - Bolarte-Arteaga, Mario

AU - Pineda-Pérez, Mario

AU - Li-Amenero, César

AU - Chávez, Haydee

AU - Bendezú, María R.

AU - García, Jorge A.

AU - Palomino-Jhong, Juan J.

AU - Ferreyra-Paredes, Carmela

AU - Melgar-Merino, Elizabeth J.

AU - Laos-Anchante, Doris

AU - Cuba-Garcia, Pompeyo A.

AU - Castillo-Romero, Patricia

AU - Yarasca-Carlos, Paulina Eliades

AU - Almeida-Galindo, José Santiago

AU - Loja-Herrera, Berta

AU - Pariona-Llanos, Ricardo

PY - 2025/5

Y1 - 2025/5

N2 - 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.

AB - 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.

KW - CYP2C8

KW - CYP3A4

KW - SLCO1B1

KW - neuropathy

KW - paclitaxel

UR - https://www.scopus.com/pages/publications/85219494347

U2 - 10.56499/jppres24.2125_13.3.955

DO - 10.56499/jppres24.2125_13.3.955

M3 - Artículo de revisión

AN - SCOPUS:85219494347

SN - 0719-4250

VL - 13

SP - 955

EP - 967

JO - Journal of Pharmacy and Pharmacognosy Research

JF - Journal of Pharmacy and Pharmacognosy Research

IS - 3

ER -