GSK461364

We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment.

The results of this study showed a significant increase in the expression level of PLK1, KIF4A, CDCA5, UBE2C, CDT1, SKA3, AURKB, and PTTG1 in TNBC compared to other BC subgroups. These genes show considerable promise as therapeutic targets for the TNBC subgroup.

PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.

In conclusion, pharmacologic PLK1 inhibition by BI6727 and GSK461364A blocked survival of CCA cells by several mechanisms. Our study provides evidence that BI6727 and GSK461364A could be alternative drugs and have potential implications at the clinical level for CCA therapy.

Current findings suggest that GSK461364A may be a chemotherapeutic agent in patients with gastric cancer. Nevertheless, more research is needed to evaluate GSK461364A as a cancer treatment drug.

Next, we studied metformin (Met) and pioglitazone (Pio)(agents in current oral cancer prevention studies) combined with G2/M blockade inhibitors, MK1775 (Wee1 kinase inhibitor) and GSK461364 (PLK inhibitor) in FA1s. Differentiation was indicated by upregulation panKeratin and Transglutaminase-3. We conclude combination therapies with high interest agents in FA-associated oral cancer can be performed in 3D culture systems and might confirm drug mechanisms of action, thus augmenting other standard methods of cancer drug evaluation and screening (e.g. cell proliferation and clonogenicity).

Additionally, high-risk patients generally exhibited higher response to chemotherapeutic agents (cisplatin, etc.). We also predicted several small molecule compounds (GSK461364, KX2-391, etc.) for treating this subset. Accordingly, this cuproptosis-relevant lncRNA signature offers an efficient approach to identify and characterize diverse prognosis, genomic alterations, and treatment outcomes in LUAD, thus potentially assisting personalized therapy.

The CTRP and PRISM-derived drug response data yielded four CTRP-derived compounds (SB-743921, GSK461364, gemcitabine, and paclitaxel) and two PRISM-derived compounds (dolastatin-10 and LY2606368). Epigenetic alterations of cancer-related genes in the tumor microenvironment play a major role in carcinogenesis. This study showed that epigenetic-related novel biomarkers could be useful in predicting prognosis, clinical diagnosis, and management in HCC.

Taken together, the present results emphasized that GSK461364A could be a useful therapeutic agent in patients with Burkitt's lymphoma. However, further studies are required to consolidate the anticancer activity of this promising compound.

Increased methylation and low expression of TREX1 were associated with SCLC cell line sensitivity to multiple Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901, as well as to the CDK inhibitor R-547, Vertex ATR inhibitor Cpd 45, and the mitotic spindle disruptor vinorelbine...Among other examples, EPAS1 (HIF2A) was associated with several Aurora kinase inhibitors, the PLK1 inhibitor GSK-461364, and the Bcl-2 inhibitor ABT-737...IGFBP5, which is expressed in the tuft cell-like SCLC subtype, was associated with the mTOR inhibitor INK-128...Methylation and expression of YAP1, a SCLC lineage driver regulating the Hippo pathway, were correlated with the MTOR inhibitor rapamycin...The 5’ UTR region of the epigenetic modifier EZH2 was associated with Aurora kinase inhibitors and the FGFR inhibitor BGJ-398. These and multiple other associations identified in this study provide a novel understanding of epigenetic mechanisms which may modulate SCLC response to chemotherapy, and suggest potential molecular targets for combination therapies. This research was supported in part with federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E.