Targeted therapies in pediatric cancers

Abstract Childhood cancers remain one of the leading causes of disease-related mortality in the pediatric population. Although multi-agent chemotherapy protocols have significantly improved survival rates, outcomes remain suboptimal in a substantial proportion of patients with high-risk, relapsed, or refractory disease. In addition, the cumulative toxicity of conventional cytotoxic agents is associated with serious long-term morbidities. Advances in genomic profiling and molecular characterization have enhanced our understanding of the biology of leukemias and solid tumors, enabling the development of more targeted therapeutic strategies with reduced systemic toxicity. In recent years, immunotherapeutic agents such as blinatumomab and inotuzumab ozogamicin, along with chimeric antigen receptor-T cell (CAR-T) cell therapy, have fundamentally transformed the treatment paradigm for relapsed and refractory acute lymphoblastic leukemia (ALL). Furthermore, targeted therapies, including tyrosine kinase inhibitors and FLT3 inhibitors, have significantly improved survival when incorporated into conventional chemotherapy regimens in both acute myeloid leukemia and high-risk ALL. In solid tumors, immune checkpoint inhibitors, targeted small molecules, and antibody-based therapies have demonstrated promising results. This review aims to summarize the current evidence on targeted therapies in pediatric leukemias, lymphomas and solid tumors, highlight ongoing clinical trials, and discuss future perspectives regarding the integration of these agents into frontline treatment strategies.