Current issues concerning drug development for pediatric hematologic malignancies.

Cure rates for pediatric hematologic malignancies (HM) have improved dramatically due to the intensive use of conventional chemotherapy and hematopoietic stem cell transplantation. However, many children still die of their disease or treatment-related toxicities. Even in patients experiencing an apparent cure, there can be significant acute and late complications of treatment. Further improvements of therapy will likely depend on the development of new therapeutic strategies. Immune-based therapy, for example monoclonal antibody-based and adoptive T-cell therapies, offers an attractive alternative that has emerged as a potent treatment strategy. Drug repositioning of molecular target drugs is now receiving remarkable attention, especially that based on recent genome wide studies. However, there are many obstacles to overcome in developing these novel drugs for pediatric patients. Pediatric drug development is difficult in itself because many of these agents are not profitable, largely due to their being too few patients, preclinical models are limited, there are too few formulations for children, special ethical considerations must be addressed when treating children and so on. Obstacles to the development of new drugs are a characteristic feature of pediatric HM. Furthermore, the approach to developing drugs for pharmaceutical approval is quite different from that to developing new therapies using approved drugs and is not well-known among investigators. Although many challenges remain in pediatric hematologic anticancer drug development, none are insurmountable.