IL-1β-plus-budesonide also recruited RELA to multiple GBRs, whereas GR was recruited to the main IL-1β-induced RBR (R4), effects that correlated with positive IL-1β/glucocorticoid transcriptional cooperativity or additivity...Cytokine-plus-glucocorticoid cotreatment revealed positive cooperative and additive interactions between GR and RELA, whereas DNA regions binding only one factor showed reduced effects on binding and transcription. These region-specific outcomes, combined with DNA looping between regulatory regions, provides insight as to how factors at multiple DNA regions may integrate their outputs to produce combinatorial regulation of apoptotic/antiapoptotic genes.

Tolinapant + RT is well tolerated and induced proliferation of activated T cells in a subset of patients. Larger prospective studies are needed to better assess efficacy.

P1, N=10, Active, not recruiting, Emory University | Recruiting --> Active, not recruiting

P1/2, N=33, Active, not recruiting, Taiho Oncology, Inc. | N=132 --> 33 | Trial primary completion date: Dec 2025 --> Dec 2024

P1, N=42, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

Our study suggests that the combination of tolinapant improves the efficacy of cell-based cancer therapies by inducing both cancer cell death and CAR-T cell proliferation. This combination therapy may overcome the current limitations of cell-based therapies and enhance their anti-cancer effect.

P1, N=42, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P1/2, N=61, Terminated, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Sep 2024 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Nov 2024; The study was terminated early due to Sponsor decision, the decision to terminate was not based on any safety concerns.

P1/2, N=230, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: Oct 2024 --> Dec 2025

P1, N=42, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Aug 2025

P1, N=33, Not yet recruiting, National Cancer Institute (NCI)

Overexpression of USP36 disrupts the formation of the XIAP-Smac complex and promotes RIPK1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in colorectal cancer progression and is a potential therapeutic target.