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Germline oncopharmacogenetics, a promising field in cancer therapy

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Abstract

Pharmacogenetics (PGx) is the study of the relationship between inter-individual genetic variation and drug responses. Germline variants of genes involved in drug metabolism, drug transport, and drug targets can affect individual response to medications. Cancer therapies are characterized by an intrinsically high toxicity; therefore, the application of pharmacogenetics to cancer patients is a particularly promising method for avoiding the use of inefficacious drugs and preventing the associated adverse effects. However, despite continuing efforts in this field, very few labels include information about germline genetic variants associated with drug responses. DPYD, TPMT, UGT1A1, G6PD, CYP2D6, and HLA are the sole loci for which the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) report specific information. This review highlights the germline PGx variants that have been approved to date for anticancer treatments, and also provides some insights about other germline variants with potential clinical applications. The continuous and rapid evolution of next-generation sequencing applications, together with the development of computational methods, should help to refine the implementation of personalized medicine. One day, clinicians may be able to prescribe the best treatment and the correct drug dosage based on each patient’s genotype. This approach would improve treatment efficacy, reduce toxicity, and predict non-responders, thereby decreasing chemotherapy-associated morbidity and improving health benefits.

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Authors and Affiliations

  1. Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Chiara Pesenti & Monica Miozzo

  2. Department of Oncology, Azienda ULSS 18, Ospedale Civile di Rovigo, Rovigo, Italy

    Milena Gusella

  3. Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy

    Silvia M. Sirchia

  4. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

    Monica Miozzo

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  1. Chiara Pesenti
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Pesenti, C., Gusella, M., Sirchia, S.M. et al. Germline oncopharmacogenetics, a promising field in cancer therapy. Cell Oncol. 38, 65–89 (2015). https://doi.org/10.1007/s13402-014-0214-4

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