Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?

Christian A. Koch, Oliver Gimm, Alexander O. Vortmeyer, Haifa K. Al-Ali, Peter Lamesch, Ott Rudolf, Regine Kluge, Uta Bierbach, Andrea Tannapfel

Research output: Chapter in Book/Report/Conference proceedingConference contribution

21 Scopus citations

Abstract

Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so-called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5-cm-large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.

Original languageEnglish (US)
Title of host publicationPheochromocytoma
Subtitle of host publicationFirst International Symposium
PublisherBlackwell Publishing Inc.
Pages517-526
Number of pages10
ISBN (Print)1573315974, 9781573315975
DOIs
StatePublished - Aug 2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1073
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Imatinib
  • Neuroendocrine
  • Neurofibromatosis type 1
  • Pheochromocytoma
  • Tumor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Koch, C. A., Gimm, O., Vortmeyer, A. O., Al-Ali, H. K., Lamesch, P., Rudolf, O., Kluge, R., Bierbach, U., & Tannapfel, A. (2006). Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy? In Pheochromocytoma: First International Symposium (pp. 517-526). (Annals of the New York Academy of Sciences; Vol. 1073). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1353.055