Pediatrics Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.
Medical Genetics Department, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.
Int J Mol Sci. 2023 Feb 28;24(5):4661. doi: 10.3390/ijms24054661.
Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.
在过去的 40 年中，儿科癌症的 5 年总生存率达到了 75-80%，对于急性淋巴细胞白血病 (ALL)，超过了 90%。白血病仍然是特定患者群体（包括婴儿、青少年和具有高风险遗传异常的患者）死亡和发病的主要原因。白血病治疗的未来需要更好地依靠分子疗法以及免疫和细胞疗法。科学界面的进步自然导致了儿童癌症治疗的进步。这些发现涉及到认识到染色体异常、癌基因扩增、肿瘤抑制基因异常以及细胞信号和细胞周期控制失调的重要性。最近，已经在成人复发/难治性 ALL 中证明有效的新型疗法正在临床试验中评估用于年轻患者。酪氨酸激酶抑制剂现在已经成为 Ph+ALL 儿科患者标准化治疗的一部分，并且在临床试验中表现出良好结果的 Blinatumomab 已获得 FDA 和 EMA 的批准用于儿童。此外，其他靶向疗法，如 Aurora 激酶抑制剂、MEK 抑制剂和蛋白酶体抑制剂，也参与了包括儿科患者的临床试验。这是从分子发现开始开发的新型白血病疗法概述，以及已应用于儿科人群的疗法。
