Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450

Pharmacogenomics is an evolving tool of precision medicine. Recently, due to the introduction of next-generation sequencing and projects generating “Big Data”, a plethora of new genetic variants in pharmacogenes have been discovered. Cancer resistance is a major complication often preventing success...

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Main Authors: Viktor Hlaváč, Petr Holý, Pavel Souček
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/10/3/108
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author Viktor Hlaváč
Petr Holý
Pavel Souček
author_facet Viktor Hlaváč
Petr Holý
Pavel Souček
author_sort Viktor Hlaváč
collection DOAJ
description Pharmacogenomics is an evolving tool of precision medicine. Recently, due to the introduction of next-generation sequencing and projects generating “Big Data”, a plethora of new genetic variants in pharmacogenes have been discovered. Cancer resistance is a major complication often preventing successful anticancer treatments. Pharmacogenomics of both somatic mutations in tumor cells and germline variants may help optimize targeted treatments and improve the response to conventional oncological therapy. In addition, integrative approaches combining copy number variations and long noncoding RNA profiling with germline and somatic variations seem to be a promising approach as well. In pharmacology, expression and enzyme activity are traditionally the more studied aspects of ATP-binding cassette transporters and cytochromes P450. In this review, we briefly introduce the field of pharmacogenomics and the advancements driven by next-generation sequencing and outline the possible roles of genetic variation in the two large pharmacogene superfamilies. Although the evidence needs further substantiation, somatic and copy number variants as well as rare variants and common polymorphisms in these genes could all affect response to cancer therapy. Regulation by long noncoding RNAs has also been shown to play a role. However, in all these areas, more comprehensive studies on larger sets of patients are needed.
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spelling doaj.art-62c835d2bebf4cc68a40fefec487559b2023-11-20T11:42:05ZengMDPI AGJournal of Personalized Medicine2075-44262020-08-0110310810.3390/jpm10030108Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450Viktor Hlaváč0Petr Holý1Pavel Souček2Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech RepublicToxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech RepublicToxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech RepublicPharmacogenomics is an evolving tool of precision medicine. Recently, due to the introduction of next-generation sequencing and projects generating “Big Data”, a plethora of new genetic variants in pharmacogenes have been discovered. Cancer resistance is a major complication often preventing successful anticancer treatments. Pharmacogenomics of both somatic mutations in tumor cells and germline variants may help optimize targeted treatments and improve the response to conventional oncological therapy. In addition, integrative approaches combining copy number variations and long noncoding RNA profiling with germline and somatic variations seem to be a promising approach as well. In pharmacology, expression and enzyme activity are traditionally the more studied aspects of ATP-binding cassette transporters and cytochromes P450. In this review, we briefly introduce the field of pharmacogenomics and the advancements driven by next-generation sequencing and outline the possible roles of genetic variation in the two large pharmacogene superfamilies. Although the evidence needs further substantiation, somatic and copy number variants as well as rare variants and common polymorphisms in these genes could all affect response to cancer therapy. Regulation by long noncoding RNAs has also been shown to play a role. However, in all these areas, more comprehensive studies on larger sets of patients are needed.https://www.mdpi.com/2075-4426/10/3/108cancer therapyresponsepharmacogenomicsATP-binding cassette transporterscytochromes P450omics
spellingShingle Viktor Hlaváč
Petr Holý
Pavel Souček
Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
Journal of Personalized Medicine
cancer therapy
response
pharmacogenomics
ATP-binding cassette transporters
cytochromes P450
omics
title Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
title_full Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
title_fullStr Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
title_full_unstemmed Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
title_short Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450
title_sort pharmacogenomics to predict tumor therapy response a focus on atp binding cassette transporters and cytochromes p450
topic cancer therapy
response
pharmacogenomics
ATP-binding cassette transporters
cytochromes P450
omics
url https://www.mdpi.com/2075-4426/10/3/108
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AT petrholy pharmacogenomicstopredicttumortherapyresponseafocusonatpbindingcassettetransportersandcytochromesp450
AT pavelsoucek pharmacogenomicstopredicttumortherapyresponseafocusonatpbindingcassettetransportersandcytochromesp450