The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options.

Vincristine (VCR), an effective antitumor drug, has been utilized in several polytherapy regimens for acute lymphoblastic leukemia, neuroblastoma and rhabdomyosarcoma. However, clinical evidence shows that the metabolism of VCR varies greatly among patients. The traditional based body surface area (BSA) administration method is prone to insufficient exposure to VCR or severe VCR-induced peripheral neurotoxicity (VIPN). Therefore, reliable strategies are urgently needed to improve efficacy and reduce VIPN. Due to the unpredictable pharmacokinetic changes of VCR, therapeutic drug monitoring (TDM) may help to ensure its efficacy and to manage VIPN. At present, there is a lot of supporting evidence for the suitability of applying TDM to VCR therapy. Based on the consensus guidelines drafted by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), this review aimed to summarize various available data to evaluate the potential utility of VCR TDM for cancer patients. Of note, valuable evidence has accumulated on pharmacokinetics variability, pharmacodynamics, drug exposure-clinical response relationship, biomarkers for VIPN prediction, and assays for VCR monitoring. However, there are still many relevant clinical pharmacological questions that cannot yet be answered merely based on insufficient evidence. Currently, we cannot recommend a therapeutic exposure range and cannot yet provide a dose-adaptation strategy for clinicians and patients. In areas where the evidence is not yet sufficient, more research is needed in the future. The precision medicine of VCR cannot rely on TDM alone and needs to consider the clinical, environmental, genetic background and patient-specific factors as a whole.

Vincristine-induced peripheral neuropathy (VIPN) is the main side effect and major reason for neuropathic pain in cancer survivors treated with vincristine. Vincristine, a chemotherapeutic antimitotic drug, is used frequently in combination chemotherapy. The primary purpose of the current study was to assess the protective effect of sodium selenite (SSe) on VIPN in vitro. Cytotoxicity effects of vincristine were evaluated using PC12 cells as a neuronal model. The cell culture studies were conducted in three groups based on the various treatments, including vincristine, SSe, and co-exposure to both compositions. Cell viability and cell cycle analyses were performed using MTT assay and flow cytometry, respectively. The level of mRNA expression of Bax and Bcl-2 was determined using qRT-PCR. According to the results, vincristine decreased the survival rate of PC12 cells. After 24 and 48 h exposure to different concentrations of vincristine (0.1-20 μΜ), the survival rate of PC12 cells decreased as compared to the control group. The results showed that treatment with 5 μΜ of vincristine resulted in apoptosis of PC12 cells. Interestingly,co-incubation of these cells with SSe significantly reduced the cell damage induced by vincristine. Furthermore, vincristine induced the inhibition of the G2 phase in PC 12 cells, and using SSe in combination with vincristine eliminated the inhibition of the cell cycle in the G2 phase. Briefly, our in vitro preliminary study showed that SSe might protect PC12 cells from vincristine-induced peripheral neuropathy during chemotherapy.