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Review
. 2023 Apr 20;13(4):695.
doi: 10.3390/jpm13040695.

Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives

Antonio Sanz-Solas  1   2 , Jorge Labrador  1   3 , Raquel Alcaraz  1 , Beatriz Cuevas  3 , Raquel Vinuesa  1 , María Victoria Cuevas  3 , Miriam Saiz-Rodríguez  1   4
Affiliations
Review

Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives

Antonio Sanz-Solas et al. J Pers Med. .

Abstract

Multiple myeloma (MM) is a hematological neoplasm for which different chemotherapy treatments are used with several drugs in combination. One of the most frequently used drugs for the treatment of MM is the proteasome inhibitor bortezomib. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection, and fatigue. This drug is almost entirely metabolized by cytochrome CYP450 isoenzymes and transported by the efflux pump P-glycoprotein. Genes encoding both enzymes and transporters involved in the bortezomib pharmacokinetic pathway are highly polymorphic. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in these possible pharmacogenetic biomarkers. In this review, we compiled all pharmacogenetic information relevant to the treatment of MM with bortezomib. In addition, we discuss possible future perspectives and the analysis of potential pharmacogenetic markers that could influence the incidence of ADR and the toxicity of bortezomib. It would be a milestone in the field of targeted therapy for MM to relate potential biomarkers to the various effects of bortezomib on patients.

Keywords: bortezomib; efficacy; multiple myeloma; pharmacogenetic biomarkers; toxicity.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
CYP pattern of cytochrome P450 hemoproteins in the human species.
See this image and copyright information in PMC

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