학술논문

Trabectedin and irinotecan combination regresses a cisplatinum-resistant osteosarcoma in a patient-derived orthotopic xenograft nude-mouse model.
Document Type
Article
Source
Biochemical & Biophysical Research Communications. May2019, Vol. 513 Issue 2, p326-331. 6p.
Subject
*EWING'S sarcoma
*OSTEOSARCOMA
*BODY size
*BONE cancer
*TUMOR growth
*HYPERTONIC saline solutions
Language
ISSN
0006-291X
Abstract
Recurrent osteosarcoma is a chemotherapy-resistant disease. Individualized precision therapy is needed for this disease. Toward this goal, we have developed the patient-derived othotopic xenograft (PDOX) mouse model of all major cancer types including osteosarcoma. Synergistic efficacy of trabectedin (TRAB) and irinotecan (IRT) has been reported in Ewing's sarcoma, soft-tissue sarcoma, and ovarian cancer. However, the efficacy of this combination on osteosarcoma is not known. The goal of present study was to determine the efficacy of the TRAB and IRT combination on cisplatinum (CDDP)-resistant osteosarcoma PDOX. The osteosarcoma PDOX models were randomized into five treatment groups of six mice: Untreated control; CDDP alone; TRAB alone; IRT alone; and TRAB and the IRT combination. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was regressed only by the TRAB-IRT combination. Tumors treated with the TRAB-IRT combination had the most tumor necrosis with degenerative change. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the TRAB and IRT combination for chemotherapy-resistant osteosarcoma. • Osteosarcoma is the most common primary malignant bone tumor. • Osteosarcoma shows resistance to mainly available drugs. • Trabectedin (TRAB) and irinotecan (IRT) combination can regress osteosarcoma PDOX. • First study shows TRAB-IRT combination is active in osteosarcoma. [ABSTRACT FROM AUTHOR]