The Current Treatment of Childhood Cancer

Dear Colleagues,

In the last four decades, the 5-year survival rate of children with cancer has increased from 58% to 83%, with the standard of care for these children relying on surgery, radiation therapy, and systemic therapy using cytotoxic agents. While cytotoxic therapies may induce complete responses in children with metastatic or relapsed tumors, however, treatment is rarely curative, and the long-term consequences of chemoradiation can be devastating. Many pediatric sarcomas are driven by fusion oncogenes resulting from chromosomal translocations (Ewing sarcoma, osteosarcoma, rhabdomyosarcoma) or by copy number changes (neuroblastoma), and recent large-scale sequencing studies (TARGET, pediatric preclinical testing consortium (PPTC), etc.) have identified frequent somatic mutations in sarcoma, neuroblastoma, and brain tumors aiding development of novel targeted therapies. Innovative approaches in pediatric oncology are aimed at enhancing the activity of chemotherapeutic agents through modulation of DNA damage response pathways. For example, the use of PARP inhibitors that exploit deficiency in homologous recombination in BRCA-deficient cancers has confirmed the concept of “synthetic lethality”. In pediatric preclinical testing, PARP inhibitors induce dramatic responses in Ewing sarcoma and acute lymphoblastic leukemia when combined with DNA-damaging agents (such as temozolomide). A great need to better understand tumor biology and screening approaches (including PDX models development) still exists, and it can be facilitated through development of immune therapies relevant to the treatment of pediatric sarcoma and through better understanding of the tumor microenvironment. Overcoming the challenges and translating them into opportunities to cure childhood cancer with acceptable quality of life will require a coordinated and global multilevel effort. Many initiatives, such as PPTC, have been committed to these goals for the past 15 years, and a new large-scale international initiative is currently under development to further enhance this effort of developing effective and less toxic treatments for children with cancer.

Dr. Raushan Kurmasheva
Guest Editor

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