A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma

Zhiying Zhang, Kaiwen Hu, Tasuku Kiyuna, Kentaro Miyake, Kei Kawaguchi, Kentaro Igarashi, Scott D. Nelson, Yunfeng Li, Shree Ram Singh, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Leiomyosarcoma is a rare and recalcitrant disease. Doxorubicin (DOX) is usually considered first-line treatment for this disease, but frequently is ineffective. In order to individualize therapy for this and other cancers, we have developed the patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we implanted a recurrent leiomyosarcoma from a resected tumor from the patient's thigh into the femoral muscle of nude mice. The following drugs were tested on the leiomyosarcoma PDOX model: DOX, the combination of gemcitabine (GEM) and docetaxel (DOC), trabectedin (TRA), temozolomide (TEM), pazopanib (PAZ) and olaratumab (OLA). Of these agents GEM/DOC, TRA and TEM were highly effective in the leiomyosarcoma PDOX model, the other agents, including first-line therapy DOX, were ineffective. Thus the leiomyosarcoma PDOX model could precisely distinguish effective and ineffective drugs, demonstrating the potential of the PDOX model for leiomyosarcoma treatment.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalPharmacological Research
Volume142
DOIs
Publication statusPublished - 2019 Apr
Externally publishedYes

Keywords

  • Chemotherapy
  • Leiomyosarcoma
  • Patient derived orthotopic xenograft (PDOX)
  • Precision medicine

ASJC Scopus subject areas

  • Pharmacology

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