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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.
- 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
- et al.
Published Web Location
https://doi.org/10.1080/15384101.2017.1423223Abstract
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 mm3: 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.
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