The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model

Takashi Higuchi, Kentaro Miyake, Norihiko Sugisawa, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Purpose: Olaratumab (OLA) is a monoclonal antibody against platelet-derived growth factor receptor alpha. OLA has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), but with limited efficacy. The goal of present study was to determine the efficacy of OLA combined with gemcitabine (GEM) and docetaxel (DOC) on a chemotherapy-resistant STS patient-derived orthotopic xenograft (PDOX). Methods: Undifferentiated soft-tissue sarcoma (USTS) from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish the PDOX model. The USTS PDOX was treated with GEM alone, GEM combined with DOC, OLA combined with DOX or GEM, and OLA combined with GEM and DOC. Tumor size and body weight were measured during the 14 days of treatment. Results: Tumor growth was arrested only by OLA combined with GEM and DOC. Tumors treated with OLA combined with GEM and DOC also had the most necrosis. Conclusions: The present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, GEM and DOC for drug-resistant soft-tissue sarcoma.

Original languageEnglish
Pages (from-to)1075-1082
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume83
Issue number6
DOIs
Publication statusPublished - 2019 Jun 1
Externally publishedYes

Keywords

  • Docetaxel
  • Doxorubicin
  • Gemcitabine
  • Olaratumab
  • Patient-derived orthotopic xenograft
  • PDOX
  • Undifferentiated soft-tissue sarcoma

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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