Peter Camaj1,2,3, Stefano Primo1, Yan Wang1,3, Volker Heinemann2,4, Yue Zhao1,3, Ruediger Paul Laubender2,5, Sebastian Stintzing2,4, Clemens Giessen-Jung2,4, Andreas Jung2,6, Sebastian Gamba1, Christiane Josephine Bruns1,2,3, Dominik Paul Modest2,4. 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.
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/SCIDmice 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.
Authors: T Yoshino; E Van Cutsem; J Li; L Shen; T W Kim; V Sriuranpong; L Xuereb; P Aubel; R Fougeray; V Cattan; N Amellal; A Ohtsu; R J Mayer Journal: ESMO Open Date: 2022-06-07
Authors: D P Modest; I Ricard; V Heinemann; S Hegewisch-Becker; W Schmiegel; R Porschen; S Stintzing; U Graeven; D Arnold; L F von Weikersthal; C Giessen-Jung; A Stahler; H J Schmoll; A Jung; T Kirchner; A Tannapfel; A Reinacher-Schick Journal: Ann Oncol Date: 2016-06-29 Impact factor: 32.976