GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.

To harness this activity, a pancreatitis-inspired nanoplatform (JT@NPs-aCD11b) co-delivering trypsinogen and the CD47 inhibitor JQ1 to TAMs is developed...Macrophage depletion abrogated efficacy, confirming TAMs as the primary mediators. This work establishes trypsinogen as a versatile immunomodulator and its nanoplatform as a promising strategy for pancreatic cancer immunotherapy.

Parallel in vivo experiments using TNBC xenograft models confirmed these findings, showing reduced IL-20RA and PD-L1 expression alongside decreased phosphorylation of JAK and STAT3. Overall, this study uncovers a novel interplay between BET inhibition and the IL-20RA/STAT3 axis, suggesting JQ1 as a valid therapeutic option for TNBC characterized by high IL-20RA expression.

A focused library of 66 heterobifunctional analogues derived from JQ1 and BI-3812 was evaluated for ternary complex formation, cellular potency, and selectivity. Computational analyses, competition experiments, and RNA sequencing indicate that the effects of the optimized analogues are driven by ternary complex formation. Together, these findings establish the linker architecture as a critical determinant of TCIP performance.

P2, N=33, Recruiting, Alexander B Olawaiye, MD | Trial completion date: Mar 2033 --> Dec 2034 | Trial primary completion date: Dec 2031 --> Nov 2033

P1, N=24, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Importantly, in vivo studies using a xenograft mouse model demonstrate significant tumor growth inhibition, with the nanoformulation + NIR irradiated group showing the most effective anti-tumor outcome with negligible hepatic, renal, and cardiac toxicities. Taken together, it may be stated that the doxorubicin/JQ1 co-loaded PBNCs might be a potential next-generation anti-TNBC theranostic agent, which combines dual-mode MRI capability and combination therapy with reduced side effects.

In addition, we demonstrate that the first bromodomain of the bromodomain and extraterminal domain-containing protein BRD4 binds to the acetylated region of interest and that this interaction is inhibited through the bromodomain and extraterminal domain inhibitor JQ1. These findings confer molecular mechanistic detail to previous observations that BRD4 and PAX3-FOXO1 colocalize at superenhancers in ARMS, adding to the growing body of literature exploring how BRD4 contacts cancer-relevant transcription factors in ways potentially relevant to the use of bromodomain and extraterminal domain inhibitors in cancer treatment.

P1, N=65, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Jun 2027 | Trial primary completion date: Apr 2026 --> Jun 2027

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

Proteomic analysis identified unique protein candidates altered in MZ-1- and SIM-1-treated KSHV-infected immortalized endothelial cells compared with (+)-JQ1-treated cells. In summary, our study develops an effective strategy against KSHV-infected immortalized endothelial cells using selective BRD PROTACs, which may help improve therapeutic outcomes for KSHV-related malignancies in the future.