Skip to main content

Advertisement

Log in

Neurofibromatosis type 1-associated wild-type gastrointestinal stromal tumor treated with anti-IGF-1R monoclonal antibody

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Gastrointestinal stromal tumors lacking mutations in KIT or PDGFRα are known as wild type (WT) and are less responsive to imatinib. These WT tumors are hypothesized to be dependent on signaling through the insulin-like growth factor 1 receptor (IGF-1R). We report the case of a 29-year-old woman with neurofibromatosis type 1–associated WT GIST treated with an anti-IGF-1R monoclonal antibody. Treatment was ineffective, and the potential basis for lack of response is discussed in the context of IGF-1R expression levels measured within this patients’ primary tumor. We suggest that future clinical trials of anti-IGF-1R therapies prospectively determine tumor IGF-1R expression levels for correlation with response to treatment.

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.

Similar content being viewed by others

References

  1. Heinrich MC, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003;21:4342–9.

    Article  PubMed  CAS  Google Scholar 

  2. Tarn C, et al. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci USA. 2008;105:8387–92.

    Article  PubMed  CAS  Google Scholar 

  3. Corless CL, Beadling C, Justusson E, Heinrich MC. Evaluation of the presence of IGF1R overexpression in wild-type and kinase mutant GI stromal tumors. J Clin Oncol. 2009;27:10506. (abstract).

    Google Scholar 

  4. Agaram NP, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008;14:3204–15.

    Article  PubMed  CAS  Google Scholar 

  5. Hartog H, Wesseling J, Boezen HM, van der Graaf WTA. The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur J Cancer. 2007;43:1895–904.

    Article  PubMed  CAS  Google Scholar 

  6. Olmos D, et al. Safety, pharmacokinetics and preliminary activity of the anti-IGF-IR antibody CP-751,871 in patients with sarcoma. J Clin Oncol. 2008;26:10501. (abstract).

    Article  Google Scholar 

  7. Patel S, et al. A SARC global collaborative phase II trial of R1507, a recombinant human monoclonal antibody to the insulin-like growth factor-1 receptor (IGF1R) in patients with recurrent or refractory sarcomas. J Clin Oncol. 2009;27:10503. (abstract).

    Google Scholar 

  8. Kurzrocki R, et al. A Phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res. 2010;16:2458–65.

    Article  Google Scholar 

  9. Miettenin M, Fetsch JF, Sobin LH, Lasota J. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 2006;30:90–6.

    Article  Google Scholar 

  10. Mussi C, Schildhaus H-U, Gronchi A, Wardelmann E, Hohenberger P. Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Clin Cancer Res. 2008;14:4550–5.

    Article  PubMed  CAS  Google Scholar 

  11. Cao L, et al. Addiction to elevated insulin-like growth factor I receptor and initial modulation of the AKT pathway define the responsiveness of rhabdomyosarcoma to the targeting antibody. Cancer Res. 2008;68:8039–48.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to F. L. Day or J. Zalcberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Day, F.L., Desai, J., Corless, C.L. et al. Neurofibromatosis type 1-associated wild-type gastrointestinal stromal tumor treated with anti-IGF-1R monoclonal antibody. Med Oncol 28 (Suppl 1), 162–164 (2011). https://doi.org/10.1007/s12032-010-9665-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9665-2

Keywords

Navigation