Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, and Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.
Cancer Discov. 2021 Mar;11(3):545-559. doi: 10.1158/2159-8290.CD-20-0779. Epub 2020 Dec 4.
The use of targeted small-molecule therapeutics and immunotherapeutics has been limited to date in pediatric oncology. Recently, the number of pediatric approvals has risen, and regulatory initiatives in the United States and Europe have aimed to increase the study of novel anticancer therapies in children. Challenges of drug development in children include the rarity of individual cancer diagnoses and the high prevalence of difficult-to-drug targets, including transcription factors and epigenetic regulators. Ongoing pediatric adaptation of biomarker-driven trial designs and further exploration of agents targeting non-kinase drivers constitute high-priority objectives for future pediatric oncology drug development. SIGNIFICANCE: Increasing attention to drug development for children with cancer by regulators and pharmaceutical companies holds the promise of accelerating the availability of new therapies for children with cancer, potentially improving survival and decreasing the acute and chronic toxicities of therapy. However, unique approaches are necessary to study novel therapies in children that take into account low patient numbers, the pediatric cancer genomic landscape and tumor microenvironment, and the need for pediatric formulations. It is also critical to evaluate the potential for unique toxicities in growing hosts without affecting the pace of discovery for children with these life-threatening diseases.
迄今为止，靶向小分子治疗药物和免疫治疗药物在儿科肿瘤学中的应用受到限制。最近，儿科批准的数量有所增加，美国和欧洲的监管举措旨在增加儿童对新型抗癌疗法的研究。儿童药物开发面临的挑战包括个别癌症诊断的罕见性和难以成药靶点（包括转录因子和表观遗传调节剂）的高流行率。目前正在对基于生物标志物的试验设计进行儿科调整，并进一步探索针对非激酶驱动因素的药物，这是未来儿科肿瘤学药物开发的首要目标。意义：监管机构和制药公司对儿童癌症药物开发的日益关注有望加速为癌症儿童提供新疗法，从而提高生存率并降低治疗的急性和慢性毒性。然而，有必要采取独特的方法来研究儿童的新疗法，考虑到患者数量少、儿科癌症基因组景观和肿瘤微环境，以及儿科制剂的需求。评估在不影响这些危及生命疾病患儿发现速度的情况下，生长宿主中潜在的独特毒性也至关重要。
