Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit in a patient-derived orthotopic xenograft (PDOX) nude mouse model. Issue 6 (19th March 2018)

• Record Type: Journal Article
• Authors: Miyake, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Masuyo; Igarashi, Kentaro; Zhang, Zhiying; Murakami, Takashi; Li, Yunfeng; Nelson, Scott D.; Elliott, Irmina; Russell, Tara; Singh, Arun; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.
• Is Part Of: Cell cycle. Volume 17:Issue 6(2018)
• Page Start: 722
• Page End: 727
• Publication Date: 2018-03-19
• Subjects: GIST -- regorafenib -- imatinib -- Gleevec -- patient-derived orthotopic xenograft -- nude mice; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2017.1423223
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit is a rare type of sarcoma. The aim of this study was to determine drug sensitivity for a regionally-recurrent case of GIST using a patient-derived orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice each when the tumor volume reached 60 mm 3 : G1, control group; G2, imatinib group (oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o., daily, for 3 weeks); G4, regorafenib (p.o., daily, for 3 weeks); G5, pazopanib (p.o., daily, for 3 weeks). All mice were sacrificed on day 22. Tumor volume was evaluated on day 0 and day 22 by laparotomy. Body weight were measured 2 times per week. Though regorafenib is third-line therapy for GIST, it was the most effective drug and regressed the tumor significantly (p < 0.001). Sunitinib suppressed tumor growth compared to the control group (p = 0.002). Imatinib, first-line therapy for GIST, and pazopanib did not have significant efficacy compared to the control group (p = 0.886, p = 0.766). The implications of this result is discussed for GIST patients.