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Future Oncol. 2015;11(13):1919-29. doi: 10.2217/fon.15.97.

KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.

Author information

1
Department of Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany.
2
German Cancer Consortium (DKTK), Heidelberg, Germany.
3
Division of Experimental Surgery, Department of Surgery, Otto-von-Guericke-University, Magdeburg, Germany.
4
Department of Medicine III, University Hospital Grosshadern, University of Munich, Munich, Germany.
5
Institute of Medical Informatics, Biometry & Epidemiology, University of Munich, Munich, Germany.
6
Institute of Pathology, University of Munich, Munich, Germany.

Abstract

AIM:

To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells.

MATERIALS & METHODS:

Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo.

RESULTS:

Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants.

CONCLUSION:

In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib.

KEYWORDS:

ELK; KRAS; MAPK pathway; colorectal cancer; regorafenib

PMID:
26161928
DOI:
10.2217/fon.15.97
[Indexed for MEDLINE]

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