The Battlefield of Chemotherapy in Pediatric Cancers

SIMPLE SUMMARY: The survival rate for pediatric cancers has improved significantly over the last decades. Conventional chemotherapies play a vital role in pediatric cancer treatment, especially in low- and middle-income countries, and the roster of chemo drugs for use in children has expanded. However, patients suffer from chemotherapy as a result of its countless side effects. Furthermore, multidrug resistance (MDR) continues to be an insurmountable obstacle that limits survival for a considerable number of patients. In this review, we discuss severe side effects in pediatric chemotherapies such as doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). Here, MDR mechanisms in chemotherapy are elucidated with the aim of improving survival, while also reducing the intensity and toxicity of chemotherapy. Furthermore, we focus on various drug transporters in common types of pediatric tumors, which could provide different therapeutic strategies. ABSTRACT: 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.