The results demonstrated the potential of using cilia-promoting drugs, such as Alvocidib and Alisertib, to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches.

P1/2, N=8, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P1/2, N=53, Terminated, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2 | Completed --> Terminated; Unable to supply investigational agent, Zotiraciclib (TG02).

P1, N=86, Completed, Prelude Therapeutics | Active, not recruiting --> Completed

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.

The CH-CCNB1 complex exhibited high stability, indicating that CH may represent potential candidate warranting further study against LC, HCC and ANT.

Importantly, co-treatments exhibited greater inhibition of tumor growth than single treatments in cell line- and patient-derived xenograft models. Taken together, our data revealed that THZ1 or TG02 enhanced in vitro and in vivo efficacy of afatinib, suggesting a potential novel combination therapeutic strategy for patients with chordoma.

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.

Moreover, intravenous administration of dCDK9-202 effectively inhibits TC-71 tumor growth without any signs of toxicity in mice. This promising CDK9 degrader dCDK9-202 has a high potential for advanced preclinical development in the treatment of CDK9-addicted human cancers.

P1, N=86, Active, not recruiting, Prelude Therapeutics | Trial primary completion date: Nov 2025 --> Jun 2025

Enitociclib also potentiates the cytotoxicity of venetoclax in relatively venetoclax-resistant KMT2A-r leukemic cells. Overall, enitociclib has shown measurable in vitro antitumor activity in KMT2A-r infant leukemia and is a rational therapeutic option to explore in future clinical trials.