KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer. (July 2015)

• Record Type: Journal Article
• Authors: Camaj, Peter; Primo, Stefano; Wang, Yan; Heinemann, Volker; Zhao, Yue; Laubender, Ruediger Paul; Stintzing, Sebastian; Giessen-Jung, Clemens; Jung, Andreas; Gamba, Sebastian; Bruns, Christiane Josephine; Modest, Dominik Paul
• Is Part Of: Future oncology. Volume 11:Number 13(2015)
• Page Start: 1919
• Page End: 1929
• Publication Date: 2015-07
• Subjects: colorectal cancer -- ELK -- KRAS -- MAPK pathway -- regorafenib; Oncology -- Periodicals; 616.99405
• DOI: 10.2217/fon.15.97
• Languages: English
• ISSNs: 1479-6694

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.