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

Author:

Zhang, Zhiying

Hu, Kaiwen

Kiyuna, Tasuko

Miyake, Kentaro

Kawaguchi, Kei

Igarashi, Kentaro

Nelson, Scott D

Li, Yunfeng

Singh, Shree Ram

Hoffman, Robert M
Author Address

AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA; Department of Surgery, University of California San Diego, CA 92103, USA; Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China., Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. Electronic address: kaiwenh@163.com., AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA; Department of Surgery, University of California San Diego, CA 92103, USA., Department of Pathology, University of California, Los Angeles, CA 90095, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: singhshr@mail.nih.gov., AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA; Department of Surgery, University of California San Diego, CA 92103, USA. Electronic address: all@anticancer.com.,

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. Copyright © 2019. Published by Elsevier Ltd.

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