Pazopanib regresses a doxorubicin-resistant synovial sarcoma in a patient-derived orthotopic xenograft mouse model

Synovial sarcoma (SS) is an aggressive subgroup of soft tissue sarcoma (STS) with high grade and high risk of metastasis. However, there are no systemic therapies available that target SS. Therefore, transformative therapy is needed for SS. To establish a patient-derived orthotopic xenograft (PDOX) model, a patient tumor with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of mice. To test the efficacy of drugs, the PDOX models were randomized into five groups: Group 1 (G1), control-without treatment; Group 2 (G2), doxorubicin (DOX); Group 3 (G3), temozolomide (TEM); Group 4 (G4), gemcitabine (GEM) combined with docetaxel (DOC); and Group 5 (G5), pazopanib (PAZ). Tumor size and body weight were measured twice a week for each treatment group. A significant growth inhibition was found on day 14 in each treatment group compared to the untreated control, except for DOX. However, PAZ was significantly more effective than both TEM and GEM+ DOC. In addition, PAZ significantly regressed the tumor volume on day 14 compared to day 0. No change was found in body weight on day 14 compared to day 0 in any treatment group. The present study demonstrated the precision of the SS PDOX models for individualizing SS therapy.