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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.


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 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.

SUBMITTER: Miyake K 

PROVIDER: S-EPMC5969563 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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 K   Kawaguchi Kei K   Kiyuna Tasuku T   Miyake Masuyo M   Igarashi Kentaro K   Zhang Zhiying Z   Murakami Takashi T   Li Yunfeng Y   Nelson Scott D SD   Elliott Irmina I   Russell Tara T   Singh Arun A   Hiroshima Yukihiko Y   Momiyama Masashi M   Matsuyama Ryusei R   Chishima Takashi T   Endo Itaru I   Eilber Fritz C FC   Hoffman Robert M RM  

Cell cycle (Georgetown, Tex.) 20180101 6


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<sup>3</sup>: G1, control group; G2, imatinib group (oral administratio  ...[more]

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