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

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

  2. Author Address

    AntiCancer, Inc., San Diego, CA, USA., Department of Surgery, University of California, San Diego, CA, USA., Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China., Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. kaiwenh@163.com., Sarcoma Oncology Center, Santa Monica, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. singhshr@mail.nih.gov., AntiCancer, Inc., San Diego, CA, USA. all@anticancer.com., Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.,
    1. Year: 2020
    2. Date: Nov 18
    3. Epub Date: 2020 11 18
  2. Journal: Scientific reports
    1. 10
    2. 1
    3. Pages: 20105
  4. Type of Article: Article
  5. Article Number: 20105
  6. ISSN: 2045-2322
  1. 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 39;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.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41598-020-76708-9
  3. PMID: 33208807
  4. View record in Web of Science®
  5. WOS: 000595721900025
  6. PII : 10.1038/s41598-020-76708-9

Library Notes

  1. Fiscal Year: FY2020-2021
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