![]() Additionally, applying the BRD4-degrading PROTAC ARV-825 and the CDK4/6 inhibitor Abemaciclib as single-agents and in synergistic combination significantly reduced TP53-altered DLBCL cell line viability. Promisingly, in vitro MDM2 inhibition with Idasnutlin and TP53 reactivation via Eprenetapopt was able to renew TNFRSF10B protein expression. Furthermore, reduced expression of CDKN1A was associated with low TNFRSF10B (FDR < 0.0001) and increased BRD4 interactant genes (FDR < 0.0001). Significant loss of CD8 T-cell presence within low-TNFRSF0B ( p = 0.0042) and altered- TP53 ( p = 0.0424) patients showcased relevant outcome-associated tumor microenvironment features. High-BRD4 and TP53 alterations were significantly associated with lower CDKN1A (p21) and TNFRSF10B (TRAIL-R2), a key tumor suppressor and CAR-T modulator, respectively. Publicly available data were analyzed for differential expression based on TP53 and 24-month event-free survival (EFS24) status, revealing enrichments of the BRD4 bromodomain oncogene ( p < 0.0001, p = 0.001). This retrospective analysis aimed to integrate various data to identify genomic partnerships capable of providing further clarity and actionable treatment targets within this population. ![]() Recently, genomic alterations and tumor microenvironment features associated with poor CAR-T response have been identified, namely those to the TP53 tumor suppressor gene. Diffuse large B-cell lymphoma (DLBCL) is a common, genomically heterogenous disease that presents a clinical challenge despite the success of frontline regimens and second-line chimeric antigen receptor T-cell (CAR-T) therapy.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |