Abstract
Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR’s clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient’s quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into individualized therapies. In this review, we discussed the potential associations between genetic variants in genes contributing to the pharmacokinetics/pharmacodynamics of VCR and VIPN incidence and severity in patients with acute lymphoblastic leukemia. Of note, genetic variants in the CEP72 gene have great potential to be translated into clinical practice. Such a genetic biomarker may help clinicians diagnose VIPN earlier. Besides, genetic variants in other genes, such as CYP3A5, ABCB1, ABCC1, ABCC2, TTPA, ACTG1, CAPG, SYNE2, SLC5A7, COCH, and MRPL47, have been reported to be associated with the VIPN, but more evidence is needed to validate the findings in the future. In fact, a variety of complex factors jointly determine the VIPN. In implementing precision medicine, the combination of genetic, environmental, and personal variables, along with therapeutic drug monitoring, will allow for a better understanding of the mechanisms of VIPN, improving the effectiveness of VCR treatment, reducing adverse reactions, and improving patients’ quality of life.
Highlights
Leukemia, the most common childhood malignant disease, is a group of diseases consisting of acute lymphocytic leukemia (ALL), chronic myeloid leukemia, and acute myeloid leukemia with large differences in morphology and cytogenetics
We focused on the genetic variability associated with the risk of developing VCR-induced peripheral neuropathy (VIPN) and we discussed different genes and genetic variants that could be involved in the pharmacokinetics and/or pharmacodynamics of VCR, which might determine the course and severity of VIPN
Plasschaert et al performed ABCB1 rs1045642 and rs2032582 (g.87531302A > T/C) variants genotyping in 52 Dutch childhood ALL patients, and the results showed no association between these two genotypes and the pharmacokinetics of VCR (Plasschaert et al, 2004)
Summary
The most common childhood malignant disease, is a group of diseases consisting of acute lymphocytic leukemia (ALL), chronic myeloid leukemia, and acute myeloid leukemia with large differences in morphology and cytogenetics. VCR is the first-line medication to treat childhood ALL (Pui and Evans, 2006). This periwinkle alkaloid is used for the treatment of solid tumors and other hematologic malignancies besides leukemia, including breast cancer and non-Hodgkin’s lymphoma (Below and Das, 2021). Cancer therapy is shifting from the traditional “one-size-fits-all” to an individualized, genetic defects-based approach, through which each patient will be diagnosed, treated, and monitored for interactions with drugs Further research established the pharmacogenomic approach as a powerful method for elucidating genetic variants for the classification of patients at low or high risk of developing chemotherapy–induced peripheral neuropathy This review summarizes the genetic variants that have been studied related to VIPN in order to guide clinicians to individualize treatment
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