KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer-Reference-Cited by-同舟云学术

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

Published:2015-07 Issue:13 Volume:11 Page:1919-1929
ISSN:1479-6694
Container-title:Future Oncology
language:en
Short-container-title:Future Oncology

Author:

Camaj Peter¹²³,Primo Stefano¹,Wang Yan¹³,Heinemann Volker²⁴,Zhao Yue¹³,Laubender Ruediger Paul²⁵,Stintzing Sebastian²⁴,Giessen-Jung Clemens²⁴,Jung Andreas²⁶,Gamba Sebastian¹,Bruns Christiane Josephine¹²³,Modest Dominik Paul²⁴

Affiliation:

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

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Oncology,General Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/fon.15.97

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