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Single-nucleotide polymorphism associations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel

    Daniel Herrero Rivera‡

    Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Seville, 41013, Spain. European University of Madrid, Madrid, 28670, Spain

    ‡Authors contributed equally

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    ,
    Carmen Garrigós Vacas‡

    Investigación Molecular y Traslacional en Oncología, Biomedicine Institute of Sevilla, IBiS/University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, 41013, Spain

    ‡Authors contributed equally

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    ,
    Laura Marcos Kovandzic

    Investigación Molecular y Traslacional en Oncología, Biomedicine Institute of Sevilla, IBiS/University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, 41013, Spain

    ,
    Javier Puente Vázquez

    Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, 28040, Spain

    ,
    Lucía A Alonso

    Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla de Santander, Santander, 39008, Spain

    ,
    Begoña Mellado González

    Department of Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona, 08036, Spain

    ,
    Verónica Calderero Aragón

    Department of Medical Oncology, Hospital de Barbastro, Huesca, 22300, Spain

    ,
    Enrique Grande

    Department of Medical Oncology, MD Anderson Cáncer Center España, Madrid, 28033, Spain

    ,
    Raquel Luque Caro

    Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs, Granada, 18014, Spain

    ,
    Juan A Virizuela Echaburu

    Department of Medical Oncology, Hospital Universitario Virgen Macarena, Seville, 41009, Spain

    ,
    Juan F Rodríguez Moreno

    Oncology Unit, HM Sanchinarro Clara Campal Comprehensive Cancer Center, Madrid, 28050, Spain

    ,
    Ainara A Etxebarria

    Department of Pathology, Hospital Universitario Marqués de Valdecilla de Santander, Santander, 39008, Spain

    ,
    Cristina Rodríguez-Antona

    Hereditary Endocrine Cancer Group, Spanish National Cancer Reaserch Center (CNIO), Madrid, 28029, Spain. ISCIII Center for Biomedical Reaserch on Rare Diseases (CIBERER), Madrid, 28029, Spain

    &
    Ignacio Durán

    *Author for correspondence: Tel.: +34 942 202 520;

    E-mail Address: Ignacioduranmartinez@gmail.com

    Investigación Molecular y Traslacional en Oncología, Biomedicine Institute of Sevilla, IBiS/University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, 41013, Spain

    Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla de Santander, Santander, 39008, Spain

    Published Online:https://doi.org/10.2217/pgs-2022-0023

    Background: The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. Results:TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12). Conclusion: Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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