A novel patient-derived orthotopic xenograft (PDOX) mouse model of highly-aggressive liver metastasis for identification of candidate effective drug-combinations

Zhiying Zhang, Kaiwen Hu, Kentaro Miyake, Tasuku Kiyuna, Hiromichi Oshiro, Sintawat Wangsiricharoen, Kei Kawaguchi, Takashi Higuchi, Sahar Razmjooei, Masuyo Miyake, Sant P. Chawla, Shree Ram Singh, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

Abstract

Liver metastasis is a recalcitrant disease that usually leads to death of the patient. The present study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model of a highly aggressive liver metastasis of colon cancer. The aim of the present study was to demonstrate proof-of-concept that candidate drug combinations could significantly inhibit growth and re-metastasis of this recalcitrant tumor. The patient’s liver metastasis was initially established subcutaneously in nude mice and the subcutaneous tumor tissue was then orthotopically implanted in the liver of nude mice to establish a PDOX model. Two studies were performed to test different drugs or drug combination, indicating that 5-fluorouracil (5-FU) + irinotecan (IRI) + bevacizumab (BEV) and regorafenib (REG) + selumetinib (SEL) had significantly inhibited liver metastasis growth (p = 0.013 and p = 0.035, respectively), and prevented liver satellite metastasis. This study is proof of concept that a PDOX model of highly aggressive colon-cancer metastasis can identify effective drug combinations and that the model has future clinical potential.

Original languageEnglish
Article number20105
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - 2020 Dec
Externally publishedYes

ASJC Scopus subject areas

  • General

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