WNTinib's efficacy was assessed in three animal models (n = 48): (a) patient-derived xenograft (PDX) HB tumors (n = 5 CTNNB1-mutant, n = 1 CTNNB1 wild-type) implanted in NSG mice; (b) PDX-derived TT001- and (c) HepG2-HB cells subcutaneously implanted in Fox1nu mice; and in two patient-derived organoids from CTNNB1-mutant HBs. In HB organoids, WNTinib demonstrated greater efficacy than standard-of-care cisplatin (P = 0.009, org-1), and its antitumor effect was further enhanced when combined with chemotherapy (P = 0.01, org-1; P = 0.007, org-22). WNTinib delays tumor progression and increases survival in CTNNB1-mutated HB models, providing rationale to explore its use in human HB.

Our findings indicate that the combination of AZD5438 and PD0325901 holds therapeutic potential for the treatment of HPV (-) HNSCC, particularly in tumors with a high mutational burden. By targeting complementary pathways, this combination may improve treatment outcomes in this aggressive cancer subtype.

This study designed and synthesized two series (A and B) of 28 unreported compounds based on rational structural modification of the lead compound AZD5438...Mechanistic studies demonstrated that B11 induces apoptosis in HCT116 cells by elevating intracellular ROS levels through suppression of anti-apoptotic protein expression and activating the caspase-3 pathway. In conclusion, compound B11 may serve as a novel selective CDK9 inhibitor worthy of further development for colorectal cancer treatment.

P1/2, N=96, Recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2029 --> Aug 2032 | Trial primary completion date: Aug 2025 --> Aug 2028

The cellular assays revealed that 13ea induced mitochondria-related apoptosis and G2/M phase arrest in cancer cells, showing superior activities compared to those of AZD-5438 (a CDK9 inhibitor) and Mocetinostat (an inhibitor of class I HDACs). Notably, the in vivo assay demonstrated that 13ea (30 mg/kg) exhibited significant inhibition on MDA-MB-231 xenograft tumor growth, with a tumor shrinkage rate of 76.83 %. In summary, we have identified 13ea as a novel CDK9/HDAC inhibitor with excellent anticancer activity in vitro and in vivo.

We posit that the combination of mitochondrial dysfunction and an inability to adapt to oxidative stress resulted in significant cell death upon ZTR treatment, ultimately increasing the therapeutic vulnerability of IDH-mutant gliomas. These findings prompted a clinical trial evaluating ZTR in IDH-mutant gliomas (NCT05588141).

P1/2, N=27, Recruiting, BeyondBio Inc. | Trial primary completion date: Aug 2023 --> Nov 2026 | Trial completion date: Jul 2024 --> Dec 2026

P1/2, N=75, Recruiting, BeyondBio Inc. | Trial primary completion date: Mar 2021 --> Nov 2026 | Unknown status --> Recruiting | Trial completion date: Oct 2021 --> Dec 2026

P1, N=12, Recruiting, BeyondBio Inc. | Trial completion date: Oct 2024 --> Dec 2026 | Trial primary completion date: Nov 2023 --> Nov 2026

We confirmed the potential importance of cell cycle-mediated regulation of C/EBPδ by showing that four of the most potent C/EBPδ activators-R547, PHA793387, AZD5438 and AT7519, all multi-cyclin-dependent kinase (CDK) inhibitors-limited the clonal expansion of PDAC cells. Next to providing a valuable selection of C/EBPδ-modulating compounds for the use in preclinical studies, this report contributes to our understanding of the molecular regulatory mechanisms of C/EBPδ in general and in PDAC in particular.

RNA-seq analyses suggested the potential modulation of the JAK2/STAT3 signaling cascade by RO-3306, a finding further confirmed by the diminished phosphorylation documented by western blotting. This study provides pivotal insights into the mechanisms governing BTKi sensitivity in DLBCL and potentially reveals new avenues for targeted therapeutic strategies.

Low numbers limit conclusive clinical outcome reporting. High PD-1 expression on post-treatment TILs encourages the addition of an immune checkpoint inhibitor to TG02 and potentially other studies of peptide vaccines in future studies.