Reference Detail

Ref Type

Journal Article

PMID

(30060824)

Authors

Kiyuna T, Murakami T, Tome Y, Igarashi K, Kawaguchi K, Miyake K, Miyake M, Li Y, Nelson SD, Dry SM, Singh AS, Russell TA, Singh SR, Kanaya F, Eilber FC, Hoffman RM

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Tissue & cell	53		2018 Aug	30-36	Tissue Cell

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References