Origins and Outcomes of the TARGET Childhood Cancer Program

A Great Need for Progress in Pediatric Cancers

Cancer is a rare but devastating disease for children and young adults. While some types of childhood cancer are considered treatable, many are still poorly understood and lack effective treatments. Furthermore, many survivors of childhood cancer experience long-term adverse effects.

When the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative began forming in 2007, there was an even greater need for improved pediatric cancer treatment and care:

• Despite increases in overall survival rates, about 20% of pediatric cancer patients did not respond well to therapy and ultimately died from their diseases. 
• The number of children and adolescents diagnosed with cancer was increasing slightly.
• Treatments were particularly harsh on growing children, often causing severe short- and long-term side effects, such as secondary cancers, physical and emotional health issues, developmental delays, and infertility.
• Treatment protocols are mostly derived from therapeutic regimens formulated for adult cancers. Genomics studies have revealed that childhood cancers can be genetically distinct from their adult counterparts, suggesting the need for alternate treatment approaches.

Building TARGET: A Collaborative Team

The TARGET initiative uses comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of hard-to-treat childhood cancers. The data generated is made available to the research community with the goal to identify therapeutic targets and prognostic markers so that novel, more effective treatment strategies can be developed and applied.

The TARGET initiative originated with two pilot projects characterizing the genomes and transcriptomes of “high-risk” subtypes of acute lymphoblastic leukemia (ALL) and neuroblastoma (NBL). The success of the two pilot project teams allowed TARGET to expand its efforts and incorporate higher resolution technologies and study additional cancer types. To date, TARGET researchers have molecularly characterized subtypes of acute myeloid leukemia, osteosarcoma, and select kidney tumors, and additional subtypes of ALL and NBL.

TARGET was built as the collaborative effort of a large, diverse consortium of extramural and NCI investigators. The team includes many members of the Children’s Oncology Group(COG), a clinical trials group devoted exclusively to childhood and adolescent cancer research. COG provided access to clinical expertise and accrued tissue materials. Over the years, TARGET researchers have worked within and across teams to generate, analyze, integrate, and interpret high-quality genomics data. The goal of working as a collaborative team including clinicians is to accelerate molecular discoveries and facilitate rapid translation of those findings into the clinic.

TARGET Outcomes and Impact

TARGET researchers have made major advances in our understanding of ALL, ultimately leading to new therapies for some of these patients using kinase inhibitors. A considerable number of children with ALL relapse following standard treatment. TARGET researchers have identified that patients with the Philadelphia chromosome-like subtype of ALL have an extremely poor prognosis, due to an activated tyrosine kinase (BCR-ABL). However, by adding the tyrosine kinase inhibitor imatinib (Gleevec) to an intensive chemotherapy regimen, the outcome of these children can be dramatically improved. 

TARGET researchers have also characterized and analyzed a number of other cancers affecting children, including neuroblastoma, intracranial rhabdoid tumors, and Wilms tumor. TARGET data and other resources are available to the greater research community for further investigation. For all data shared through TARGET, patient confidentiality and privacy are protected. This data sharing approach allows investigators outside the initiative to use the data, thereby increasing the chance that novel therapeutics will be developed and benefit children with cancer.