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Doxorubicin-resistant pleomorphic liposarcoma with PDGFRA gene amplification is targeted and regressed by pazopanib in a patient-derived orthotopic xenograft mouse model

  1. Author:
    Kiyuna, Tasuku
    Murakami, Takashi
    Tome, Yasunori
    Igarashi, Kentaro
    Kawaguchi, Kei
    Miyake, Kentaro
    Miyake, Masuyo
    Li, Yunfeng
    Nelson, Scott D
    Dry, Sarah M
    Singh, Arun S
    Russell, Tara A
    Singh, Shree Ram
    Kanaya, Fuminori
    Eilber, Fritz C
    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, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Division of Hematology-Oncology, University of California, Los Angeles, CA, USA., Division of Surgical Oncology, University of California, Los Angeles, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Division of Surgical Oncology, University of California, Los Angeles, CA, USA. Electronic address: fceilber@mednet.ucla.edu., AntiCancer Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2018
    2. Date: Aug
    3. Epub Date: 2018 05 22
  2. Journal: Tissue & Cell
    1. 53
    2. Pages: 30-36
  4. Type of Article: Article
  1. Abstract:

    Pleomorphic liposarcoma (PLPS) is a heterogeneous resistant group of tumors. Complete surgical resection is the only known way to treat PLPS. PLPS is reristant to both radiation and chemotherapy. Therefore, precise individualized therapy is needed to improve outcome of advanced PLPS patients. In this study, a patient-derived orthotopic xenograft (PDOX) model of a PDGFRA-amplified PLPS was established in the biceps femoris of nude mice by surgical orthotopic implantation (SOI) in order to match the patient. The PLPS PDOX was treated with pazopanib (PAZ) which targets PDGFRA, as well as with temozolomide (TEM) and first-line therapy doxorubicin (DOX). The PLPS PDOX was resistant to DOX and responded very well to PAZ as well as TEM. The tumor volume on treatment day-14 relative to day-1 was as follows: DOX (4.50?±?2.6, p?=?0.8087); PAZ (1.29?±?0.9, p?=?0.0008 compared to the control, p?=?0.0167 compared to DOX); TEM (1.07?±?0.8, p?=?0.0079 compared to the control, p?=?0.0079 compared to DOX). There was no significant difference in body weight between any treated group or control. The PAZ- and TEM-treated tumors showed extensive necrosis compared to the DOX-treated and untreated PDOX tumors. The present study showed that PDGFRA amplification could be effectively targeted by PAZ. The PLPS PDOX model also identified the efficacy of TEM which does not target PDGFRA, indicating that the PDOX model can identify effective targeted therapy as well as standard therapy and at the same time, identify ineffective drugs, even if they are first-line. Published by Elsevier Ltd.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.tice.2018.05.010
  3. PMID: 30060824
  4. View record in Web of Science®
  5. WOS: 000440173900005
  6. PII : S0040-8166(18)30177-0

Library Notes

  1. Fiscal Year: FY2017-2018
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