Pediatric Cancers -- Clinical Research Program

Our pediatrics team is at the forefront of developing new treatments for a variety of pediatric cancers, including leukemias, lymphomas, brain tumors, neuroblastoma, bone cancer, and retinoblastoma, among others. We are at the leading edge of both basic science and clinical research in investigating the causes of and new treatments for pediatric cancers.

Our research team includes specialists who focus solely on pediatric cancers, including medical and radiation oncologists, radiologists, and surgeons. In addition, we have conducted extensive research on the long-term side effects of treatments for pediatric cancer, following patients for decades after they have been cured.

Our extensive involvement in the Children's Oncology Group and our leadership of the recently established Pediatric Oncology Experimental Therapeutic Consortium (POETIC) ensures the flow of information between the Pediatrics Disease Management Team and national cooperative efforts.

Among our recent research accomplishments:

Long-Term Follow-Up

  • We found that most young women at an increased risk of breast cancer due to chest radiation treatment for childhood cancer are not following breast cancer screening recommendations. JAMA. 2009 Jan 28;301(4):404-14. [PubMed Abstract]

Molecular Pathology

  • We found that the RET oncogene is a critical component of transcriptional programs associated with the differentiation of neuroblastic tumors. The core set of retinoic acid-regulated genes includes essential molecular components of pathways necessary for neuroblastic tumor differentiation. These components have potential as therapeutic targets and molecular markers of response to differentiating agents. Mol Cancer Ther. 2007 Apr;6(4):1300-9. [PubMed Abstract]
  • We used integrative genomics to identify distinct molecular classes of neuroblastoma and showed that multiple genes are affected by regional alterations in DNA copy number. These data support the hypotheses that chromosomal deletion events in this cancer likely target multiple genes through alteration in mRNA dosage. The potential multiplicity of transcripts involved has significant implications for ongoing gene discovery strategies. Cancer Res. 2006 Jun 15;66(12):6050-62. [PubMed Abstract]
  • We analyzed the global gene-expression profiles of the two major subtypes of pediatric rhabdomyosarcomas, which are alveolar (ARMS) and embryonal (ERMS). The gene-expression signature of ARMS provides a source of potential diagnostic markers, therapeutic targets, and PAX-FKHR downstream genes, and can be used to reliably distinguish these sarcomas from ERMS. J Pathol. 2007 Jun;212(2):143-51. [PubMed Abstract]
  • We found that pediatric gastrointestinal stromal tumors (GISTs) have a distinct transcriptional signature, suggesting a biology that is different from GISTs in adults. Also, in vitro drug screening showed that second-generation kinase inhibitors may provide greater clinical benefit in pediatric GISTs. Clin Cancer Res. 2008 May 15;14(10):3204-15. [PubMed Abstract]
  • After conducting a comprehensive analysis of the DNA of locoregional neuroblastoma tumors, we determined that clonal ploidy heterogeneity is a marker with prognostic significance. Genes Chromosomes Cancer. 2007 Apr;46(4):385-96. [PubMed Abstract]
  • We examined whether common polymorphisms in candidate genes involved in the pharmacodynamics of anthracyclines had an impact on the risk of anthracycline-related congestive heart failure (CHF). We found that the functional CBRs V244M polymorphism may affect the risk of anthracycline-related CHF among childhood cancer survivors by modulating the intracardiac formation of cardiotoxic anthracycline alcohol metabolites. This warrants large case-control studies to confirm. Cancer. 2008 Jun 15;112(12):2789-95. [PubMed Abstract]
  • A study of retinoblastoma tumor cells found evidence of impairment in antifolate transport. Analysis also suggests that trimetrexate will be a more effective chemotherapy agent than methotrexate. This supports consideration of a phase II study to determine the effectiveness of trimetrexate for recurrent intra-ocular retinoblastoma. Pediatr Blood Cancer. 2008 Mar;50(3):573-6. [PubMed Abstract]
  • We found new cases of the Ewing family of tumors with rare EWS fusions, including two with EWS-ETV1, one with EWS-FEV, and a fourth case in which we cloned a novel EWS-SP3 fusion — the first known cancer gene fusion involving a gene of the Sp zinc finger family. Analysis of these new cases, along with data on nine previously reported cases with fusions of EWS to ETV1, E1AF, or FEV, suggest a strong predilection for these primitive small round cell sarcomas with rare EWS fusions to arise in extraskeletal primary sites. J Mol Diagn. 2007 Sep;9(4):498-509. [PubMed Abstract]
  • We investigated the status of parathyroid hormone type 1 receptor (PTHR1) PTHrP/PTHR1 and its possible role in osteosarcoma. We found evidence suggesting that PTHR1 overexpression may promote osteosarcoma progression by conferring a more aggressive phenotype and forming a more favorable microenvironment. Int J Cancer. 2007 Sep 1;121(5):943-54. [PubMed Abstract]
  • We used genomewide expression arrays to identify novel markers for subclinical disease for the Ewing family of tumors. Detection of STEAP1, CCND1, or NKX2-2 transcription factor mRNA in blood mononuclear cells provides a reliable indicator of minimal residual disease. These markers may be informative at diagnosis for risk-group assessment, and their clinical utility can now be tested in large patient cohorts. Clin Cancer Res. 2007 Dec 1;13(23):6978-83. [PubMed Abstract]
  • We developed novel markers for subclinical metastatic disease for the Ewing family of tumors. Clin Cancer Res. 2007 Dec 1;13(23):6978-83. [PubMed Abstract]
  • We developed a ten-gene microarray-based predictor that distinguished alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) with approximately 95 percent accuracy both in our data by cross-validation and in an independent validation using a published dataset of 26 samples. The gene-expression signature of ARMS provides a source of potential diagnostic markers, therapeutic targets, and PAX-FKHR downstream genes, and can be used to reliably distinguish these sarcomas from ERMS. J Pathol. 2007 Jun;212(2):143-51. [PubMed Abstract]

Targeted Therapies

  • We demonstrated through in vitro drug screening that the second-generation kinase inhibitors nilotinib, sunitinib, dasatinib, and sorafenib are more effective than imatinib against wild-type KIT and that second-generation kinase inhibitors may provide greater clinical benefit in pediatric GISTs than imatinib. Clin Cancer Res. 2008 May 15;14(10):3204-15. [PubMed Abstract]


New Agents

  • A study found that adding muramyl tripeptide to chemotherapy for patients with osteosarcoma resulted in improved survival and a trend toward better event-free survival. Also, the addition of ifosfamide to the three-drug chemotherapy of cisplatin, doxorubicin, and methotrexate did not enhance event-free survival or overall survival. J Clin Oncol. 2008 Feb 1;26(4):633-8. [PubMed Abstract]
  • We found that 2-chlorodeoxyadenosine is an active agent in patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis (LCH). The finding suggests that the agent should be further evaluated in a prospective multicenter trial for LCH patients with enhancing mass lesions of the central nervous system. Pediatr Blood Cancer. 2008 Jan;50(1):72-9. [PubMed Abstract]


Drug Combinations and Multimodal Treatments

  • We found that early intensification therapy improves survival for high-risk acute lymphoblastic leukemia in children.
  • A member of our team participated in a study showing that intensive induction chemotherapy followed by autologous marrow rescue in young children with newly diagnosed supratentorial primitive neuroectodermal tumors appears to not only improve event-free survival and overall survival but also successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients. Pediatr Blood Cancer. 2008 Feb;50(2):312-8. [PubMed Abstract]