This work establishes cuproptosis induction via NP@Fla-Cu as a transformative strategy against UM, effectively addressing challenges in tumor selectivity and off-target toxicity. The dual functionality of flavopiridol as a copper ionophore and mitophagy activator provides a promising combinatorial approach to overcome therapy resistance in immunosuppressive malignancies.

P1, N=84, Terminated, MEI Pharma, Inc. | Recruiting --> Terminated; Business reasons, not related to safety or efficacy results.

P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

In cellular assays, HS34 displayed potent antiproliferative activity against TNBC cells, outperforming the reference inhibitor KB-0742...Furthermore, HS34 exhibits favorable DMPK properties, including high oral bioavailability and metabolic stability, which align with the significant antitumor efficacy observed in an orally treated xenograft model. Collectively, these findings establish HS34 as a selective CDK9 inhibitor and demonstrate that exploiting target-specific conformational features offers an effective strategy for kinase selectivity.

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.