Genetic factors influencing the development of vincristine-induced neurotoxicity

ABSTRACT

Introduction: One of the most common side effects during vincristine (VCR) use is the establishment of VCR–induced peripheral neuropathy (VIPN). Among several risk factors that can influence the development of VIPN, such as cumulative dose and patient’s age, sex, ethnicity, and genetic variants, this review is focused on the genetic variability.

Areas covered: A literature research was performed firstly using the following PubMed search string ((((CIPN OR (vincristine AND neurotoxicity OR (vincristine AND neuropathy))) AND (polymorphisms OR (genetic variants OR (genetic factors OR (genetic profile OR (pharmacogenetics OR (genome-wide OR (genetic risk OR (expression genotype))))))))))) but also other relevant papers cited by the selected articles were included. Based on the obtained results, we identified two main categories of genes: genes involved in pharmacokinetics (genes related to metabolism and transport) or pharmacodynamics (genes related to mechanism of action) of VCR.

Expert opinion: Despite several clinical retrospective studies investigating the possible correlations between patient genotype and VIPN onset, contrasting and inconsistent results are reported.

In conclusion, given the clinical relevance of VIPN, further and more focused research would be fundamental in order to identify genetic variants able to predict its development and to allow a safer management of treated patients.

KEYWORDS:

• Neurotoxicity
• pharmacogenetic
• polymorphisms
• risk factors
• vincristine

Article highlights

• One of the most common side effects during vincristine treatment is the establishment of chemotherapy–induced peripheral neuropathy.

• Cumulative dose, age, sex, ethnicity, and genetic variants of patients might influence the development of vincristine-induced peripheral neuropathy.

• Genes involved in pharmacokinetics or pharmacodynamics of vincristine are investigated in most studies analyzing the possible correlation between genomic variants and vincristine-induced peripheral neurotoxicity.

• Pharmacogenetic potentially would be an instrument to predict interindividual response to treatment and useful to personalize therapy management, but the available results are still inconsistent.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript received funding from PRIN (Progetti di ricerca di Rilevante Interesse Nazionale) 2017 (grant: 2017ZFJCS3).