Therapeutically Applicable Research to Generate Effective Treatments (TARGET)

Addressing a 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 TARGET initiative began forming in 2007, there was an even greater need for improved pediatric cancer treatments and care. 

Building TARGET

The TARGET initiative used comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of hard-to-treat childhood cancers. The data generated was made available to the research community with the goal to identify therapeutic targets and prognostic markers that would enable the development of effective treatment strategies.

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

TARGET and Collaboration

TARGET was built as a collaborative effort with extramural researchers and intramural NCI investigators. 

The team also included many members of the Children’s Oncology Group (COG), which provided access to clinical expertise and accrued tissue materials. 

Over the years, TARGET researchers worked within and across teams to generate, analyze, integrate, and interpret high-quality genomics data. The collaborative goal was to accelerate molecular discoveries and facilitate rapid translation of those findings into the clinic.

TARGET Outcomes and Impact

TARGET researchers 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 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 also characterized and analyzed a number of other cancers affecting children, including neuroblastoma, intracranial rhabdoid tumors, and Wilms tumor. 

Additionally, TARGET data and other resources are available to the research community for further investigation. 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.

Data collected and processed by the TARGET program is available at the Genomic Data Commons (GDC). 

Analysis files from TARGET Publications can be found in the “Supplemental Data” Section of GDC Publication Pages.

Authors who use data from TARGET should reference the TARGET dataset in accordance with the Data Use Certification posted at dbGaP. 

We suggest the following language for citations:

"The results published here are in whole or part based upon data generated by the Therapeutically Applicable Research to Generate Effective Treatments initiative, phs000218. The data used for this analysis are available at the Genomic Data Commons (https://portal.gdc.cancer.gov)."

Insufficient understanding of the biology of many childhood cancers limits the development of novel treatments for these young patients. Pan-cancer model systems, such as cell lines and xenografts, have been used in basic research to help expand the knowledge of cancer mechanisms and treatment response. 

Few model systems of pediatric cancers have been available to the research community. To address this need, TARGET developed the Pan-Cancer Model Systems initiative to create models of high-risk or hard-to-treat childhood cancers.

Several of TARGET’s disease-specific projects were able to produce tumor cell lines or xenografts, with or without matched normal comparators, as well as some noncancerous tissues from the same organ. 

Models produced by the Pan-Cancer Model Systems initiative include:

• Acute leukemia cell lines and xenografts with matched primary and/or relapsed tumor information
• Embryonic stem cell lines (sequenced for some TARGET disease projects)
• Kidney tumor cell lines
• Neuroblastoma cell lines and xenografts with matched controls
• Normal brain tissues

Additionally, TARGET provided whole exome sequencing for 131 cell lines and xenografts from NCI’s Pediatric Preclinical Testing Program (PPTP).

For additional information about the TARGET, please contact Dr. Liming Yang.