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Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts.

Publication ,  Conference
Keir, ST; Roskoski, MA; Wagner, S; Tiedt, R; Bigner, DD; Friedman, HS
Published in: Cancer Research
April 15, 2013

INTRODUCTION: INC280 is an oral, highly selective c-Met receptor tyrosine kinase inhibitor. The hepatocyte growth factor (HGF)-c-Met pathway is one of the most frequently dysregulated pathways in human cancers. Aberrant HGF-c-Met signaling has been documented in a wide range of human malignancies. The c-Met pathway can be activated by abnormal HGF and c-Met expression levels, c-Met activating mutations and gene amplifications. At this time, INC280 is in development for the treatment of solid tumors with activation of the c-Met pathway. As a part of this study, we looked at the antitumoral activity of INC280 in adult glioblastoma (GBM) brain tumor xenografts with elevated levels of Met or HGF expression.METHODS: Met expression and copy number was determined by ELISA and qPCR, HGF mRNA by RT-qPCR. Adult GBM tumor xenografts were grown subcutaneously in athymic BALB/c mice. After tumor size reached 200-500 mm3 subcutaneously, groups of 10 mice were randomly treated with either drug vehicle/control or INC280 (10mg/kg BID) PO for 30 days. Tumor responses for subcutaneous xenografts were assessed by tumor growth delay and regression.RESULTS: Based on activation of the c-Met pathway, the following two xenograft lines were selected for treatment with INC280: D-09-0337 MG and D-09-0477 MG. As a single agent, INC280 demonstrated statistically significant (p<0.001) growth delays of 40.23 and 30.13 days in D-09-0337 MG and D-09-0477 MG, respectively. In addition, when treated with INC280, tumors implanted with D-09-0337 MG (10 out of 10) or D-09-0477 MG (4 out of 10) regressed.CONCLUSION: Our results demonstrate the therapeutic efficacy of the inhibition of a c-Met receptor tyrosine kinase in adult brain tumor xenografts with activation of the c-Met pathway. These results warrant further exploration of INC280 in clinical trials for the treatment of adult brain tumor patients with dysregulated proto-oncogene c-Met and its ligand HGF.Citation Format: Stephen T. Keir, Martin A. Roskoski, Sabrina Wagner, Ralph Tiedt, Darell D. Bigner, Henry S. Friedman. Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2079. doi:10.1158/1538-7445.AM2013-2079

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2013

Volume

73

Issue

8_Supplement

Start / End Page

2079 / 2079

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
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MLA
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Keir, S. T., Roskoski, M. A., Wagner, S., Tiedt, R., Bigner, D. D., & Friedman, H. S. (2013). Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts. In Cancer Research (Vol. 73, pp. 2079–2079). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2013-2079
Keir, Stephen T., Martin A. Roskoski, Sabrina Wagner, Ralph Tiedt, Darell D. Bigner, and Henry S. Friedman. “Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts.” In Cancer Research, 73:2079–2079. American Association for Cancer Research (AACR), 2013. https://doi.org/10.1158/1538-7445.am2013-2079.
Keir ST, Roskoski MA, Wagner S, Tiedt R, Bigner DD, Friedman HS. Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts. In: Cancer Research. American Association for Cancer Research (AACR); 2013. p. 2079–2079.
Keir, Stephen T., et al. “Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts.Cancer Research, vol. 73, no. 8_Supplement, American Association for Cancer Research (AACR), 2013, pp. 2079–2079. Crossref, doi:10.1158/1538-7445.am2013-2079.
Keir ST, Roskoski MA, Wagner S, Tiedt R, Bigner DD, Friedman HS. Abstract 2079: Antitumoral activity of INC280 against adult glioblastoma brain tumors xenografts. Cancer Research. American Association for Cancer Research (AACR); 2013. p. 2079–2079.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2013

Volume

73

Issue

8_Supplement

Start / End Page

2079 / 2079

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis