A novel patient-derived orthotopic xenograft (PDOX) mouse model of highly-aggressive liver metastasis for identification of candidate effective drug-combinations.
- Resource Type
- Academic Journal
- Authors
- Zhang Z; 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.; Hu K; Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. kaiwenh@163.com.; Miyake K; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Kiyuna T; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Oshiro H; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Wangsiricharoen S; AntiCancer, Inc., San Diego, CA, USA.; Kawaguchi K; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Higuchi T; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Razmjooei S; AntiCancer, Inc., San Diego, CA, USA.; Miyake M; AntiCancer, Inc., San Diego, CA, USA.; Department of Surgery, University of California, San Diego, CA, USA.; Chawla SP; Sarcoma Oncology Center, Santa Monica, CA, USA.; Singh SR; Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. singhshr@mail.nih.gov.; Hoffman RM; AntiCancer, Inc., San Diego, CA, USA. all@anticancer.com.; Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.
- Source
- Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
- Subject
- Language
- English
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.