PLK4 (Polo Like Kinase 4)

P2, N=15, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2025 --> Dec 2026

In vivo experiments demonstrated that U07 could inhibit tumor growth in a dose-dependent manner, with the high-dose group (6 mg) showing an anti-tumor effect comparable to that of cisplatin, and it could downregulate the expression of PLK4 and GPX4 in tumor tissues. In conclusion, the oridonin derivative U07 exerts anti-gastric cancer effects by inhibiting cell proliferation, inducing apoptosis, and mediating ferroptosis via PLK4, providing a new candidate drug and therapeutic target for gastric cancer treatment.

Discoidin I-like domain 3 is a novel gene with a potentially key role in BA-related liver fibrosis, possibly influencing the proliferation and apoptosis of cholangiocytes by regulating the PI3K-AKT signaling pathway, thereby participating in the occurrence and development of liver fibrosis. This study provides new insights into the molecular mechanisms and potential treatment strategies for BA.

Overall, our results demonstrate that in addition to its known nuclear localization, McIdas also localizes to centrioles, affecting centriole duplication. This novel, direct role of McIdas in centriole duplication connects its functions in cell cycle regulation and multiciliogenesis.

Given their unique properties and clinical relevance, PGCCs represent a promising frontier in cancer biology with the potential to overcome therapeutic resistance and prevent tumor recurrence through targeted interventions. This review seeks to elucidate the role of PGCCs across multiple cancer types and highlights their emerging potential as novel targets for future cancer therapies.

Additionally, we have summarized studies showing the association of PLK4 with multiple cancers and how its modulation affects cancer progression. Further, we have discussed PLK4 inhibitors and molecular pathways that could be associated with PLK4 and can open new avenues in cancer management.

Genomic analyses of cancer cell line data reveal a negative correlation between FBXW7 expression and aneuploidy, as well as a positive correlation between FBXW7 and STIL expression at the mRNA level. Our results thus contribute to improved understanding of the molecular basis of centrosome amplification and aneuploidy.

In order to find commonly expressed differentially expressed genes (DEGs) in a variety of TNBC cell lines treated with docetaxel (GSE70690), paclitaxel (GSE86839), doxorubicin (GSE202536), and cisplatin (GSE77515), as well as untreated TNBC cell lines (GSE38959), bioinformatics approaches were used. The identified DEGs and pathways in this study shed light on possible therapeutic targets and reducing drug resistance. These findings contribute to the development of personalized and targeted therapies for TNBC, ultimately leading to improved patient outcomes.

Structural analysis of multiple X-ray cocrystal structures enabled the design of analogs that demonstrated excellent kinome selectivity. Tumor regression was observed in efficacy studies of compound 25 in a CHP-134 neuroblastoma xenograft tumor model.

Moreover, we identified simvastatin as a potent inhibitor of CDT1, effectively inhibiting CDT1-mediated centrosome amplification and PGCC formation. In summary, our findings reveal a critical role for CDT1 in driving centrosome amplification and PGCC formation through activation of the PLK4/SASS6 axis, which subsequently contributes to therapeutic resistance and malignant progression.

TRIM37 expression is associated with increased cell proliferation, regardless of subtype; however, it is strongly associated with reduced immune activity, worse response to chemotherapy, and poor prognosis in ER-positive/HER2-negative BC, whereas it was associated with better response to chemotherapy and no relationship with survival in TNBC. Our results provide critical insights into the clinical application of TRIM37-targeted therapies.

Various compounds, such as CFI-400945, centrinone B, and others have been developed to inhibit PLK4 activity...Clinical studies have been initiated with some of these compounds in cancer patients, including those with breast cancer. This manuscript discusses the role of PLK4 as a promising therapeutic target in breast cancer, one of the most common causes of morbidity and mortality in women.