Integrated Study of Clinical, Molecular Analysis, Mr-Based Radiogenomic, and Preclinical Trials for Precision Treatment of Atypical Teratoid/Rhabdoid Tumor (Atrt) in Children(2/3)

Atypical teratoid rhabdoid tumor (ATRT) is an entity of highly malignant CNS embryonal tumor that occurs mainly in infants. The treatment outcome is very poor by upfront conventional chemotherapy. The survival improves after upfront high dose chemotherapy (HDC) or after upfront radiation therapy (RT). However, both HDC and RT cause deterioration neurocognitive function and quality of life in young kids. The development of effective but protective innovative treatment of is a necessity. Since 2016, several important papers regarding (epi-) genomic studies were reported and three molecular subgroups (ATRT-TYR, ATRT-SHH, ATRT-MYC) are classified. There are clinical, upregulated gene/pathway, and therapeutic target different among subgroups. This research project is based on a series of clinical and basic research on childhood ATRTs from 2000 to 2018 including preliminary clinical data retrieving and analysis, preliminary RNA-Seq and analysis, the establishment of a PDX/PDOX mice model and tumor cell line from the primary and recurrent tumor in a patient, and the experience of integrating clinical, molecular analysis, and MR-based radiogenomics research on pediatric medulloblastomas. The targets of this project are: (1) Cohort series analysis of clinical variables and prognostic factors. (2) Genomic and epigenomic profiling/analysis of tumor for prognostic and therapeutic gene identification of tumors in Taiwan. (3) To identify general and subgroup based therapeutic targets and drugs for in vitro and in vivo studies. (4) To establish primary and recurrent ATRT PDX/PDOX mice model, primary cancer, and tumor cell line for in vitro and in vivo drug testing. (5) To apply MR-based radiogenomics to identify imaging features with prognostic significance and gene expression pattern correlation. The aim of this project is to establish clinical, molecular, MR-radiomics, and outcome based risk stratification of ATRT and the correlated precision/optimal treatment. The results of this project may be expanded for domestic multicenter and Asia multicenter collaborative research.