Devyani Goswami, Amity University Kolkata
CRISPR-CAS9 a huge discovery in the biomedical field which guarantees curing various genetic disorders has been used and a topic of research among various scientists. Due to this the scientists discovering CRISPR-CAS9 were awarded the Nobel Prize of Chemistry, 2020. Utilizing this concept a group of scientists tried to treat the faulty gene which causes atypical teratoid rhabdoid tumor (ATRT). ATRT is an incurable pediatric brain tumor.
For this study, seven human ATRT cell lines: BT12, BT16, CHLA02, CHLA04, CHLA05, CHLA06, CHLA266 were considered; out of BT12, BT16, CHLA06, CHLA266 were considered to be the best cell lines to be used after further studies and observations. A genome-wide CRISPR-CAS9 knockout was done to obtain the genetic dependencies in ATRT. It was concluded that 245 out of 671 genes had druggable categories and 37 out of the 245 genes could be modulated with clinically available compounds like CDKs, RTKs, regulators of p53 signaling.
The study further claims that the inactivation of SMARCB1 is the sole recurrent genetic driver in ATRT and all the cell lines were very sensitive to the alterations in the p53 signaling pathway. The CDK4/6 inhibitors have been claimed to be the most important method for molecular driven therapies in ATRT, for showing their efficacy in ATRT cells over non-ATRT cells. The CDK4/6 inhibitors show a mutual dependency with each other in ATRT cells.
This study awaits further clinical trials to be used as a therapeutic for all. More studies on the CDK4/6 inhibitors requires more research and clinical approaches.
Also read: Variation of SARS-CoV-2 genomes in populations due to RNA editing enzymes
REFERENCE: Genome wide CRISPER and small molecule screens uncover targetable dependencies in ATRThttps://doi.org/10.1101/2020.12.09.417378
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