Skip to main content

Advertisement

Log in

Educational paper

The development of new therapies for pediatric oncology

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Although cure rates for children with cancer are approximately 70%, improvements in cure rates have slowed in the past decade, likely due to our inability to further improve outcome using currently available drugs. Novel drug approaches are needed for children with difficult-to-treat malignancies, such as stage IV neuroblastoma, sarcomas, brain tumors, and relapsed leukemia. Several novel agents show promise for improving outcome in patients with either high risk or recurrent disease. For leukemia, inhibitors of cell cycle progression, such as clofarabine and nelarabine, have shown great promise in their ability to increase treatment efficacy in high-risk disease. Targeted agents such as tyrosine kinase inhibitors, DNA binding compounds (trabectedin), and monoclonal antibodies (GD2 inhibitors for neuroblastoma and anti-CD22 antibodies for pre-B acute lymphocytic leukemia (ALL)) also show promise for future treatment. Extensive reviews of each of these agents are presented elsewhere; this article provides an overview of molecular agents at different stages of FDA/EMA approval; those that are currently approved for use in children, currently approved for use in adults, as well as those that show promise in early clinical trial testing, or are supported by strong preclinical data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Berg SL, Blaney SM, Devidas M et al (2005) Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol 23:3376–3382

    Article  PubMed  CAS  Google Scholar 

  2. Brown P, Small D (2004) FLT3 inhibitors: a paradigm for the development of targeted therapeutics for paediatric cancer. Eur J Cancer 40:707–721

    Article  PubMed  CAS  Google Scholar 

  3. Brown P, Smith FO (2008) Molecularly targeted therapies for pediatric acute myeloid leukemia: progress to date. Paediatr Drugs 10:85–92

    Article  PubMed  Google Scholar 

  4. Cai X, Gray PJ Jr, Von Hoff DD (2009) DNA minor groove binders: back in the groove. Cancer Treat Rev 35:437–450

    Article  PubMed  CAS  Google Scholar 

  5. Carter NJ, Keam SJ (2010) Trabectedin: a review of its use in soft tissue sarcoma and ovarian cancer. Drugs 70:355–376

    PubMed  CAS  Google Scholar 

  6. De Angelo DJ (2009) Nelarabine for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Hematol Oncol Clin North Am 23:1121, vii-viii

    Article  Google Scholar 

  7. Dileo P, Grosso F, Casanova M et al (2007) Trabectedin (T) in metastatic Ewing's family tumors (EFT) patients (pts) progressing after standard chemotherapy. J Clin Oncol 18:10040

    Google Scholar 

  8. Faderl S, Gandhi V, Keating MJ et al (2005) The role of clofarabine in hematologic and solid malignancies—development of a next-generation nucleoside analog. Cancer 103:1985–1995

    Article  PubMed  CAS  Google Scholar 

  9. Giamas G, Man YL, Hirner H et al (2010) Kinases as targets in the treatment of solid tumors. Cell Signal 22:984–1002

    Article  PubMed  CAS  Google Scholar 

  10. Hijiya N, Gaynon P, Barry E et al (2009) A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia 23:2259–2264

    Article  PubMed  CAS  Google Scholar 

  11. Hingorani P, Kolb EA (2010) Past, present and future of therapies in pediatric sarcomas. Future Oncol 6:605–618

    Article  PubMed  CAS  Google Scholar 

  12. Jeha S (2009) Recent progress in the treatment of acute lymphoblastic leukemia: clofarabine. Hematol Oncol Clin North Am 23:1137–1144, viii

    Article  PubMed  Google Scholar 

  13. Jeha S, Gaynon PS, Razzouk BI et al (2006) Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol 24:1917–1923

    Article  PubMed  CAS  Google Scholar 

  14. Jin S, Gorfajn B, Faircloth G, Scotto KW (2000) Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation. Proc Natl Acad Sci USA 97:6775–6779

    Article  PubMed  CAS  Google Scholar 

  15. Knapper S, Burnett AK, Littlewood T et al (2006) A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 108:3262–3270

    Article  PubMed  CAS  Google Scholar 

  16. Kushner BH, Kramer K, Cheung NK (2001) Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. J Clin Oncol 19:4189–4194

    PubMed  CAS  Google Scholar 

  17. Larson RA (2007) Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine. Semin Oncol 34:S13–S20

    Article  PubMed  CAS  Google Scholar 

  18. Lau L, Supko JG, Blaney S et al (2005) A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clin Cancer Res 11:672–677

    PubMed  CAS  Google Scholar 

  19. Maris JM (2010) Recent advances in neuroblastoma. N Engl J Med 362:2202–2211

    Article  PubMed  CAS  Google Scholar 

  20. Modak S, Cheung NK (2010) Neuroblastoma: therapeutic strategies for a clinical enigma. Cancer Treat Rev 36:307–317

    Article  PubMed  CAS  Google Scholar 

  21. Mussai F, Campana D, Bhojwani D et al (2010) Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. Br J Haematol 150:352–358

    Article  PubMed  CAS  Google Scholar 

  22. Paz-Ares L, Lopez-Pousa A, Poveda A et al (2010) Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone. Invest New Drugs [ePub ahead of print] PMID: 20960029

  23. Richardson PG, Mitsiades C, Hideshima T, Anderson KC (2006) Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med 57:33–47

    Article  PubMed  CAS  Google Scholar 

  24. Rossler J, Geoerger B, Taylor M, Vassal G (2008) Small molecule tyrosine kinase inhibitors: potential role in pediatric malignant solid tumors. Curr Cancer Drug Targets 8:76–85

    Article  PubMed  Google Scholar 

  25. Siegel D, Hussein M, Belani C et al (2009) Vorinostat in solid and hematologic malignancies. J Hematol Oncol 2:31

    Article  PubMed  Google Scholar 

  26. Stam RW, den Boer ML, Pieters R (2006) Towards targeted therapy for infant acute lymphoblastic leukaemia. Br J Haematol 132:539–551

    Article  PubMed  CAS  Google Scholar 

  27. Tan J, Cang S, Ma Y et al (2010) Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. J Hematol Oncol 3:5

    Article  PubMed  Google Scholar 

  28. Tuscano JM, Riva A, Toscano SN et al (1999) CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood 94:1382–1392

    PubMed  CAS  Google Scholar 

  29. Wan X, Helman LJ (2007) The biology behind mTOR inhibition in sarcoma. Oncologist 12:1007–1018

    Article  PubMed  Google Scholar 

  30. Yu AL, Gilman AL, Ozkaynak MF et al (2010) Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 363:1324–1334

    Article  PubMed  CAS  Google Scholar 

  31. Zwaan CM, den Boer MB, Beverloo HB et al (2007) Dasatinib (SPRYCEL®) in children and adolescents with relapsed or refractory leukemia: preliminary results of the CA180018 phase I/II study from the ITCC Consortium. Blood 110:1049

    Google Scholar 

Download references

Conflict of interest

The authors have no financial conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Terzah M. Horton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Horton, T.M., Berg, S.L. Educational paper. Eur J Pediatr 170, 555–559 (2011). https://doi.org/10.1007/s00431-010-1374-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-010-1374-5

Keywords

Navigation