Research prospect of preclinical model construction and precision therapy in ameloblastoma
10.3760/cma.j.cn112144-20230703-00264
- VernacularTitle:成釉细胞瘤临床研究前模型构建及精准治疗研究前景
- Author:
Xindan KANG
1
;
Lulu SUN
;
Zhiyuan ZHANG
;
Shuyang SUN
Author Information
1. 上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科 上海交通大学口腔医学院 国家口腔医学中心 国家口腔疾病临床医学研究中心 上海市口腔医学重点实验室 上海市口腔医学研究所 中国医学科学院口腔颌面再生医学创新单元,上海 200011
- Keywords:
Ameloblastoma;
Preclinical model;
Organoid;
Gene mutation;
Personalized treatment
- From:
Chinese Journal of Stomatology
2023;58(8):844-851
- CountryChina
- Language:Chinese
-
Abstract:
Ameloblastoma (AM) is a benign odontogenic tumor with unknown etiology. It is prone to recurrence and has a potential for malignant transformation. Patients often show high rates of relapse after curettage, or suffer from structural and functional damage of jaw after partial resection. Whole-genome sequencing data revealed that BRAF mutations and SMO mutations were common and likely to be mutually exclusive in AM. It was also reported that BRAF inhibitors were effective in several patients carrying BRAF V600E mutation. However, reliable preclinical models are urgently needed for exploring targeted therapy as it′s so difficult to conduct large clinical trials in this tumor. Patient-derived cell models in vitro and xenograft models in vivo are frequently used preclinical models. In fact, benign tumor cells generally showed a finite proliferative capacity in two-dimensional culture, and most likely, they could exhibit altered cellular phenotype after immortalization. Moreover, this benign tumor presented low chances of subcutaneous engraftment in nude mice. Accordingly, humanized mouse xenograft model needs more exploration. Yet, it is worth mentioning that a three-dimensional organoid model presents a high potential in culturing stem-cell-like epithelial cells in AM, and it would further be used in recapitulating corresponding tumors and developing targeted medicines. In this paper, we review research progress in preclinical models and the genetic variations of AM, and raise drug screening prospect of the current organoid models, which may pave the way for the possible personalized medicine in AM.