National Cancer Institute (NCI) TARGET: Therapeutically Applicable Research to Generate Effective Treatments

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative seeks to accelerate research in novel marker and drug development, along with understanding the molecular basis of pediatric malignancy, through identification of genomic changes associated with the following childhood cancers:

• Acute Lymphoblastic Leukemia (ALL) - A fast-growing type of blood cancer in which too many immature white blood cells are found in the blood and bone marrow.
• Acute Myeloid Leukemia (AML), including AML Induction Failure cases (AML-IF) - Another type of blood cancer marked by too many myeloblasts, an alternate type of immature white blood cell, are found in the blood and bone marrow. Upon diagnosis, AML patients without high-risk genetic markers undergo standard chemotherapy regimen, called the primary induction phase, to eliminate most cancer cells and induce a remission state.
• Clear Cell Sarcoma of the Kidney (CCSK) - A rare type of kidney cancer, in which the inside of the cells looks clear when viewed under a microscope. Clear cell sarcoma can spread from the kidney to other organs, most commonly the bone, but also including the lungs, brain, and soft tissues of the body.
• Neuroblastoma (NBL) - Cancer of cells of the sympathetic nervous system.
• Cancer Model Systems (MDLS), including PPTP - MDLS includes acute leukemia cell lines and xenografts with matched primary and/or relapsed tumor information, NBL cell lines and xenografts with matched controls, kidney tumor cell lines, normal brain tissues, and embryonic stem cell lines that were sequenced for some TARGET disease projects.
• Osteosarcoma (OS) - A cancer of the bone that primarily affects children and adolescents.
• Rhabdoid Tumor (RT) - A rare, fast-growing cancer that usually forms in the kidney or central nervous system (the brain and spinal cord) but can also form in soft tissues in other areas of the body. Rhabdoid tumors tend to spread quickly, are hard to treat, and have a poor prognosis.
• Wilms' Tumor (WT) - A cancer of cells in the kidney that can spread to the liver, lung and lymph nodes.

More information can be found about each TARGET subproject by following the links on the top of this page.

Together these cancers account for the majority of the more than 10,000 childhood cancer cases diagnosed in the United States each year.

TARGET has employed a set of advanced and complementary genome analysis technologies, including large scale 2nd and 3rd generation genome sequencing, to strategically characterize alterations in both gene expression and in genomic structure (such as deletions and amplification) that are involved in childhood cancers. The goal of this coordinated effort has been to create a comprehensive genomic and transcriptomic profile of each cancer. Integrated analysis of the TARGET data has identified those genes that are either altered in their expression level or mapped to the chromosome regions of deletion/amplification/translocation, as these genes represent strong candidates for therapeutic targeting. To learn more about the TARGET project, which is now completed, visit the website at http://ocg.cancer.gov/programs/target.

TARGET primary genomic sequencing datasets (controlled-access) and limited phenotype data (open-access) are available from this site and the NCBI's Sequence Read Archive (SRA). TARGET's raw sequencing data can also be accessed at the NCI's Genomic Data Commons (GDC). TARGET datasets generated by the original TARGET research teams, including fully annotated clinical information, higher-level (analyzed) molecular characterization data (e.g. gene expression, copy number variation, epigenetics, targeted sequencing) are available via the TARGET Data Matrix as well as from each of the TARGET Publication Pages at the GDC (Please see the "Supplemental Links" section of any TARGET publication's "Publication Information and Associated Data Files page" at the GDC.). GDC-generated analyzed data files for TARGET are also available from the GDC's Data Portal. Please see the TARGET Publication Guidelines at the OCG website for updated details on sharing of any TARGET substudy data.

• Study Weblinks:
  • TARGET Data Matrix
• Study Design:
  • Tumor vs. Matched-Normal
• Study Type:
  • Cohort
• Total number of consented subjects: 6319
• Subject Sample Telemetry Report (SSTR)

TARGET employs stringent criteria for inclusion while focusing on primary untreated pediatric tumors. All cases included for TARGET must include a matched normal sample with a tumor specimen from the same patient. All samples used within TARGET are reviewed by a pathologist who confirms the accuracy of cancer diagnosis, as well as the presence of at least 70-80% tumor nuclei with no more than 20-30% necrotic tissue.

Each cancer being studied has disease-specific inclusion and exclusion criteria for the cohorts being characterized and sequenced. Additional details can be found on the TARGET website, particularly within the TARGET Data Matrix.

Pediatric ALL was the first disease to be piloted for the TARGET initiative, which is jointly managed by the NCI Office of Cancer Genomics (OCG) and Cancer Therapy Evaluation Program (CTEP). The study is run as a cooperative collaboration between investigators and management staff at NCI, Children's Oncology Group, University of Colorado Cancer Center, University of New Mexico Cancer Center, and St. Jude Children's Research Hospital.

• Primary Phenotype: Neoplasms
• Acute Lymphoblastic Leukemia
• Leukemia, Myeloid, Acute
• Neuroblastoma
• Osteosarcoma
• Wilms Tumor
• Clear Cell Sarcomas
• Rhabdoid Tumor
• Xenografts

• Children's Oncology Group (COG; Tissues for TARGET are collected as part of COG clinical and biological protocols)
  • Peter C. Adamson, MD. Children's Hospital of Philadelphia, Philadelphia, PA, USA.
• Principal Investigator (ALL Project Team)
  • Stephen P. Hunger, MD. University of Colorado Cancer Center, Denver, CO, USA.
• Principal Investigators (AML Project Team)
  • Soheil Meshinchi, MD, PhD. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Robert Arceci, MD, PhD. Children's Hospital, Phoenix, AZ, USA.
• Principal Investigator (NBL Project Team)
  • John M. Maris, MD. Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Robert Seeger, MD. Children's Hospital of Los Angeles, Los Angeles, CA, USA.
  • Javed Khan, MD. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
• Principal Investigator (OS Project Team)
  • Ching Lau, MD, PhD. Texas Children's Hospital, Houston, TX, USA.
  • Paul Meltzer, MD, PhD. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
• Principal Investigator (Kidney Project Teams - WT, CCSK, RT)
  • Elizabeth J. Perlman, MD. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
• Principal Investigator (Cell Lines and Xenografts - PPTP)
  • Peter Houghton, PhD. The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.