Peccatori Nicolò, Brivio Erica, Lissat Andrej, Bautista Sirvent Francisco, Salzer Elisabeth, Biondi Andrea, Fazio Grazia, Rizzari Carmelo, Tasian Sarah K, Zwaan Christian Michel
Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy.
School of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy.
Cancers (Basel). 2025 Oct 15;17(20):3322. doi: 10.3390/cancers17203322.
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.
在过去几十年中，急性白血病的生物学和遗传学特征取得了重大进展，风险适应性多药治疗方案也得到了优化，这极大地提高了急性淋巴细胞白血病（ALL）患儿的治愈率和生活质量。尽管取得了这些理想的结果，但复发或化疗难治（R/R）疾病或具有高危遗传特征的患者仍然面临不尽人意的结局。进一步强化传统化疗在实现预期疗效而不产生过度副作用方面已达到极限，因此需要创新方法来提高治愈率，同时继续尽量减少与化疗和造血干细胞移植相关的毒性。在精准医学时代，血液肿瘤学领域出现了两种关键治疗策略：分子靶向治疗和免疫治疗。基于抗体的细胞免疫治疗无疑重塑了儿童ALL的治疗格局，并且在当前和未来的一线治疗方案中具有发挥主导作用的巨大潜力；这些重要疗法在最近的综述中有详细阐述。分子靶向小分子抑制剂疗法仍然是精准医学的基石，下一代测序技术的最新进展为其提供了支持，这些进展使得转录组和基因组分析数据能够应用于风险分层和治疗优化。针对ALL患儿的临床试验有助于完善治疗方法并改善治疗效果，随着治疗策略日益复杂，这一模式仍然至关重要。这篇综述聚焦于儿童ALL的分子靶向治疗方法，旨在总结已完成临床试验的结果，以突出正在进行和即将开展的试验的现状，并为精准驱动优化儿童B-ALL和T-ALL治疗的未来方向提供见解。
