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Olaratumab combined with doxorubicin and ifosfamide overcomes individual doxorubicin and olaratumab resistance of an undifferentiated soft-tissue sarcoma in a PDOX mouse model

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

  2. Author Address

    AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., AntiCancer, Inc., San Diego, CA, USA., Department of Surgery, University of California, San Diego, CA, USA. Electronic address: mbouvvet@ucsd.edu., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan. Electronic address: tsuchi@med.kanazawa-u.ac.jp., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2019
    2. Date: Jun 1
    3. Epub Date: 2019 03 10
  2. Journal: Cancer letters
    1. 451
    2. Pages: 122-127
  4. Type of Article: Article
  5. ISSN: 0304-3835
  1. Abstract:

    Olaratumab (OLA), a monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFRa), has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), with limited efficacy. The goal of present study was to determine the efficacy of OLA in combined with doxorubicin (DOX) and ifosfamide (IFO) on STS. 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 an undifferentiated soft-tissue sarcoma (USTS) patient-derived orthotopic xenograft (PDOX) model. USTS PDOX tumors were treated with OLA alone, DOX alone, DOX combined with IFO, OLA combined with DOX or IFO, and OLA combined with DOX and IFO. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was arrested by OLA combined with DOX and IFO. Tumors treated with OLA combined with DOX and IFO had the most necrosis. The present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, DOX and IFO for soft-tissue sarcomas. Published by Elsevier B.V.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.canlet.2019.03.003
  3. PMID: 30867142
  4. View record in Web of Science®
  5. WOS: 000464297000012
  6. PII : S0304-3835(19)30146-6

Library Notes

  1. Fiscal Year: FY2018-2019
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