P1/2, N=70, Recruiting, Ellipses Pharma | Trial completion date: Dec 2025 --> Dec 2026

Lung adenocarcinoma patients have poorer prognosis due to higher levels of CPCs, TMPO-AS1, and E2F1. A sponge complex between TMPO-AS1 and hsa-let-7b-5p may contribute to the tumor progression, and targeting CPCs with natural compounds could offer therapeutic potential. Highlights 1. The overexpression of chromosomal passenger complex genes, AURKB, BIRC5, CDCA8, and INCENP is significantly associated with poor prognosis in lung adenocarcinoma (LUAD), particularly among smokers. 2. The competing endogenous RNA (ceRNA) axis, which involves the long non-coding RNA TMPO-AS1 and the miRNA hsa-let-7b-5p, regulates the expression of these CPC genes. TMPO-AS1 shows a positive correlation with CPC genes, while hsa-let-7b-5p shows a negative correlation. 3. Survival analysis indicates that the combined expression of CPC genes, TMPO-AS1, hsa-let-7b-5p, and E2F1 may serve as a reliable prognostic biomarker panel for LUAD in smokers. 4. Hesperidin exhibits a strong binding affinity to CPC proteins, particularly AURKB, when compared to Barasertib, Docetaxel, and Paclitaxel, highlighting its potential as a therapeutic agent. 5. The overexpression of CPC genes, E2F1, and TMPO-AS1 in LUAD is strongly associated with reduced infiltration of CD4⁺ T cells, indicating their role in promoting an immunosuppressive tumor microenvironment.

Besides, downregulating the levels of c-Myc, BCL-xL and MCL-1 also contributed to the synergistic effects of the combined regimen on t-FL. Taken together, these findings suggest that the synergy between the DGKα inhibitor ritanserin and multi-targeted inhibitor chiauranib might represent a promising option for the treatment of t-FL.

P2, N=36, Active, not recruiting, Advenchen Pharmaceuticals, LLC. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells.

Overall, compound 18 is a valuable chemical biology tool and a potential therapeutic. Our findings suggest that pharmacological degradation of AURKB could offer an alternative therapeutic approach for treating AURKB-dependent tumors.

Furthermore, G-749 is screened and identified as a novel NAT10 inhibitor capable of effectively impeding lysosomal acidification and tumor metastasis by disrupting the NAT10-Ubiquitin-specific Peptidase 39 (USP39) interaction. Overall, the results unveil a novel role of ac4C modifications in regulating lysosomal acidification and propose a potential strategy by targeting NAT10 to inhibit esophageal cancer metastasis.

Alisertib and barasertib emerge as potential in vitro candidates against MM, although further studies are needed to validate their efficacy and to find the best combinations with other molecules.

Furthermore, treatment with the drugs dasatinib and AT-9283 were associated with an inhibition of CIAO1 expression in gastric cancer cells, and decreased rates of tumor spread and invasion. Taken together, the findings of the present study suggest that CIAO1 is a promising biomarker both for assessing prognosis and evaluating the tumor immune microenvironment of gastric cancer.

Finally, our drug screening identified barasertib, an aurora kinase inhibitor, as a triple-combination candidate with epidermal growth factor receptor-tyrosine kinase inhibitors and XAV-939 for MYC+ cells. This study demonstrates the utility of longitudinal pharmacogenomic analysis to develop treatment strategies according to individual tumor evolution type. The study underscores the importance of integrating genomic and pharmacogenomic profiling in clinical practice to tailor treatments according to tumor evolution type.

The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC.

This study is the first to demonstrate that morin inhibits CRC progression by targeting the AURKB-UCHL3 axis to regulate autophagy-dependent ferroptosis, providing experimental evidence for its therapeutic potential in CRC treatment.