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Resistance to platinum-based cancer drugs: a special focus on epigenetic mechanisms

    Yuselin Mora‡

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    ‡Authors contributed equally

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    ,
    María Elena Reyes‡

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, 8370003, Chile

    ‡Authors contributed equally

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    ,
    Louise Zanella

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    ,
    Bárbara Mora

    Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Temuco, 4810101, Chile

    ,
    Kurt Buchegger

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    Departamento Ciencias Básicas, Facultad de Medicina, Universidad de La Frontera, Temuco, 4811230, Chile

    ,
    Carmen Ili

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    &
    Priscilla Brebi

    *Author for correspondence:

    E-mail Address: brebimieville@gmail.com

    Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile

    Published Online:https://doi.org/10.2217/pgs-2021-0020

    Chemoresistance is a significant clinical challenge, limiting the drug response in cancer. Several mechanisms associated with drug resistance have been characterized, and the role of epigenetics in generating resistance to platinum-based drugs has been clarified. Epigenetic mechanisms such as DNA methylation, histone modification, long noncoding RNA, and microRNA affect the expression of genes implicated in absorption, distribution, metabolism and excretion (ADME) of drugs, and other non-ADME genes that encode enzymes involved in the processes of cell proliferation, DNA repair, apoptosis and signal transduction key in the development of chemoresistance in cancer, specifically in platinum-based drugs. This review summarizes current discoveries in epigenetic regulation implicated in platinum drug resistance in cancer and the main clinical trials based on epigenetic therapy, evaluating their potential synergy with platinum-based drugs.

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