In the past decades, significant advancements in the biological and genetic characterization of acute leukemias and optimization of risk-adapted multi-agent treatment protocols have dramatically improved cure rates and quality of life for children with acute lymphoblastic leukemia (ALL). Despite these optimal results, patients with relapsed or chemotherapy-refractory (R/R) disease or with high-risk genetic features still face unsatisfactory outcomes. Further intensification of conventional chemotherapy has reached its limits in achieving the desired efficacy without undue side effects, necessitating innovative approaches to improve cure rates while continuing to minimize the toxicities associated with chemotherapy and hematopoietic stem cell transplantation. In the era of precision medicine, two key therapeutic strategies have emerged in hemato-oncology: molecularly targeted therapies and immunotherapies. Antibody-based and cellular immunotherapies have undoubtedly reshaped the landscape of childhood ALL treatment and have significant potential to play leading roles in current and future frontline regimens; these important therapies are well delineated in recent reviews. Molecularly targeted small molecule inhibitor therapies remain a cornerstone of precision medicine, supported by recent advancements in next-generation sequencing, which have enabled the application of transcriptomic and genomic profiling data to risk stratification and therapy optimization. Clinical trials for children with ALL have been instrumental in refining therapies and improving outcomes, a paradigm that remains critical as treatment strategies become increasingly complex. This comprehensive review focuses upon molecularly targeted therapy approaches for childhood ALL and aims to summarize findings from completed clinical trials to highlight the current landscape of ongoing and upcoming trials and to provide insights into future directions for the precision-driven optimization of pediatric B-ALL and T-ALL treatment.
过去几十年间，急性白血病生物学与遗传学特征的深入研究以及风险分层多药联合治疗方案的优化，显著提高了儿童急性淋巴细胞白血病（ALL）的治愈率和生活质量。尽管已取得这些理想成果，但复发/难治性（R/R）或具有高危遗传特征的患者仍面临疗效不佳的困境。传统化疗方案的进一步强化在疗效提升与毒副作用控制之间已达到平衡极限，亟需创新治疗策略在提高治愈率的同时持续降低化疗及造血干细胞移植相关毒性。在精准医疗时代，血液肿瘤领域已形成两大核心治疗策略：分子靶向治疗与免疫治疗。抗体药物与细胞免疫疗法无疑重塑了儿童ALL的治疗格局，在当前及未来一线治疗方案中具有重要潜力，近期综述已对这些关键疗法进行了系统阐述。分子靶向小分子抑制剂疗法作为精准医疗的基石，在二代测序技术发展的推动下，通过转录组与基因组图谱数据实现了风险分层与治疗方案的精准优化。儿童ALL临床试验在治疗方案优化和疗效提升方面发挥了关键作用，随着治疗策略日益复杂化，这一研究范式的重要性愈发凸显。本综述聚焦儿童ALL分子靶向治疗领域，系统总结已完成临床试验的研究成果，重点阐述当前进行中及即将开展试验的最新进展，并对B-ALL和T-ALL精准治疗优化的未来发展方向提出见解。
肿瘤(癌症)患者之家