Abstract 4609: Establishment of sarcoma PDX models with various subtypes for drug efficacy evaluation

Abstract

Abstract Sarcomas are the neoplasms which arise in bone and peri-osseous soft tissues. Osteosarcoma, Ewing’s sarcoma and Chondrosarcoma are the 3 major malignancies of bone sarcoma affecting both children and adults. Among those, osteosarcoma is the most common bone-originated cancer in young ages. Although the primary tumor is often surgically resected and the improvements in therapeutic strategies were achieved in recently years, the outcomes remain poor with 50-60% of 5-year survival rates because of relapses mainly due to the metastases, especially metastases to lung. Soft tissue sarcomas are mesenchymal neoplasms including different histologic subtypes which can arise from viscera such as genitourinary, gastrointestinal or gynecologic organs, or from nonviscera soft tissues such as muscle, adipose, synovium etc. Among various subtypes of soft tissue sarcoma, synovial sarcoma is an aggressive malignancy that accounts for 10%-20% of soft tissue sarcoma in young population. Surgical excision combined with adjuvant or neoadjuvant radiotherapy provides a good treatment of local disease, but the recurrences often occurs with the most common pattern of metastasis to lung. Despite the increasing risk of sarcoma and poor outcome, effective treatments, especially precision therapies, are largely lacking. Breakthrough drug discovery is hindered by limited numbers of suitable in vivo models. In recent decades, patient-derived xenograft (PDX) mouse models are commonly used for drug efficacy evaluation with prominent advantages of similar histopathology and molecular pathology with patient tumors. We have established a series of patient derived xenograft models, recapitulating diverse subtypes of sarcoma, including bone sarcoma and soft tissue sarcoma. More than 30 osteosarcoma PDX models are established with a wide spectrum of age populations and clinical grades. Half of these osteosarcoma PDX models are derived from children and young adults. 2 of these osteosarcoma PDX models are derived from relapse tumors and 5 of them are from metastatic tumors (mainly from lung metastases). Besides, we have also established one Ewing’s sarcoma (derived from a 9-years-old child) and 5 Chondrosarcoma PDX models. We have also collected numbers of soft tissue sarcoma samples, of which, we have established 9 synovial sarcoma PDX models, mostly derived from adult patients with 2 of them derived from lung metastatic tumors. Among these PDX models derived from metastasis tumors, we also have established several matched PDX models with their primary tumors. Taken together, our established sarcoma PDX models include different subtypes and different cancer stages (especially primary vs. metastatic tumors), providing a valuable preclinical platform for the understanding of different pathogenesis, as well as supporting drug discovery efforts on different subtypes of sarcomas. Citation Format: Jessie Jingjing Wang, Mengxiong Sun, Likun Zhang, Yingqi Hua, Henry Qixiang Li, Davy Xuesong Ouyang. Establishment of sarcoma PDX models with various subtypes for drug efficacy evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4609.