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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine
Last Updated: 10/01/2014


Prioritizing Targeted Agents for Pediatric Clinical Evaluation

Identifying molecularly targeted agents that may be effective for specific childhood cancers is critical for the success of CTEP-sponsored pediatric clinical trials. CTEP supports two initiatives in support of this objective: the Pediatric Preclinical Testing Program (PPTP) and the Childhood Cancer TARGET (Therapeutically Applicable Research to Generate Effective Treatments) Initiative. The PPTP, described above, tests specific targeted agents against its panel of molecularly characterized childhood cancer preclinical models. The TARGET Initiative, which is a collaborative effort with the NCI Office of Cancer Genomics, systematically applies genomic characterization methods to identify genes that are recurrently altered in specific childhood cancers, under the hypothesis that these altered genes provide therapeutically relevant insights into the pathways on which cancers depend for growth and survival. The TARGET Initiative ( focuses on five different childhood cancers: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), neuroblastoma, high-risk Wilms tumor, and osteosarcoma.

Discoveries through the ALL TARGET Initiative include identifying the poor outcome associated with IKZF1 (Ikaros) alterations, identifying activating JAK family mutations in high-risk B-precursor ALL, and identifying novel gene fusions involving the CRLF2 gene in a subset of patients with high-risk B-precursor ALL. The initial translation of these discoveries into the clinic includes the development of a COG Phase 1 Consortium clinical trial of a JAK inhibitor for children with relapsed ALL.

Other clinical trials building upon TARGET and PPTP findings include studies of the following agents:

  • Bcl-2 family inhibitor ABT-263 in children with ALL (in development),
  • Aurora A kinase inhibitor MLN8237 for children with ALL and neuroblastoma,
  • MEK inhibitor AZD6244 for children with recurrent pilocytic astrocytoma,
  • Oncolytic virus SVV-001 for children with recurrent solid tumors, and
  • Combination of the mTOR inhibitor temsirolimus with standard agents for rhabdomyosarcoma.