Application of patient derived xenograft model in personalized drug screening for chondrosarcoma of head and neck: A preclinical study

Abstract

Objectives

The effect of radiotherapy and chemotherapy on head and neck chondrosarcoma (HNCS) has not been unanimously determined because of the rarity of HNCS. Patient-Derived Xenograft (PDX) model is considered to be a good preclinical model for new drug development and personalized drug screening. We performed this study to investigate the preclinical application and value of PDX model in drug screening for HNCS.

Materials and methods

Tumor tissues of a patient with HNCS who underwent surgical treatment in the Department of Head and Neck Oncology of our hospital were collected. The PDX model was established in NCG mice and successfully passed to the P3 generation in nude mice. After the tumor grew to a certain size, three drugs targeting different molecules (Nilotinib, Regorafenib, Rapamycin) were given respectively. The treatment efficiency and safety were observed.

Results

NCG mouse is a kind of mouse that can successfully establish the PDX model of HNCS, and the PDX model can be stably passed in nude mice. The PDX tumor show similar histopathological characteristics to the parent tumors. After stable passaging, the mesenchymal cells were reduced and the tumor cells were increased in PDX tumor, making it easier to extract primary tumor cells. In the P3 PDX tumor, oral administration of nilotinib and regorafenib or intraperitoneal injection of rapamycin could significantly reduce the tumor size.

Conclusion

For rare tumors such as HNCS, PDX model is a good preclinical model for personalized drug screening and has good clinical application value.