TTK (TTK Protein Kinase)

TTK drives TNBC progression by orchestrating G1/S and G2/M transitions and sustaining β-catenin-Cyclin D1 signaling. Its restricted expression in normal tissues, combined with oncogenic effects, positions TTK as a promising prognostic biomarker and therapeutic target. Pharmacological inhibition of TTK, potentially combined with β-catenin pathway inhibitors, may offer an effective strategy for TNBC treatment.

BRU inhibites GC progression by targeting P4HA2, disrupting glycolysis-histone lactylation signaling, and downregulating TTK. This metabolic-epigenetic mechanism positions BRU as a promising natural therapeutic for GC.

The glycolysis-CCNB2-H3K18la-TTK/BUB1B signaling axis exacerbates the malignant progression of PDAC, providing insights into potential lactylation-based therapeutic strategies for this disease.

Cisplatin resistance is a major contributor to treatment failure in ovarian cancer (OC). Molecular dynamics simulations demonstrated that hesperidin, cissamine and tetrandrine exhibited strong binding affinities toward AURKA, vitamin D receptor, and TTK. Future studies are encouraged to focus on the experimental validation of these compounds and delve deeper into the possible mechanisms of drug resistance, aiming to improve their therapeutic effectiveness and real-world applicability.

High glucose increases the expression of p-DRP (Ser616) by inhibiting p-AMPK and subsequently affecting mitochondrial fission and lactic acid levels. This process is likely prompted by lactation levels of histone H3 and the expression of BUB1B and TTK.

Here, we extended those studies into syngeneic murine models of TNBC using two TTK inhibitors: empesertib and the novel TTK inhibitor CFI-402257 (also known as luvixasertib) that was recently granted FDA fast track approval in breast cancer. Taken together, these studies demonstrate that TTK inhibition enhances radiosensitivity and TTK inhibition with RT modulates the immune landscape of TNBC. Collectively, this combination may represent a novel therapeutic strategy to improve outcomes for patients with TNBC by both direct tumor cytotoxicity and by promoting an immune-responsive environment.

Finally, a xenograft mouse model showed that TTK significantly promotes MM development. In summary, we demonstrated that the TTK-RGN axis regulates cell apoptosis, G0/G1 phase arrest, and proliferation in MM, highlighting TTK as a potential target for therapeutic intervention in this cancer.

CFI-402257, a specific inhibitor of TTK, is found to exhibit anti-tumor effects and exerted synergistic efficacy with PI3K inhibitor, Duvelisib, in TCL. The study shows that TTK contributes to the development of TCL by regulating p38α-mediated AMPK/mTOR pathway. CFI-402257 is expected to be a promising strategy for TCL treatment.

High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.

Which implies that TTK is an oncogene in HER2 + BRCA and is a valuable research target.

The CTRGPS enhances early diagnosis and treatment precision in BC, improving clinical outcomes. TTK, a key gene in the signature, shows promise as a therapeutic target, supporting the CTRGPS's potential clinical utility.

Notably, the results of the present study revealed that DEPDC1 upregulated RAS expression through TTK and enhanced ERK activity, thereby affecting glycolysis and autophagy in OS cells. Collectively, the present investigation demonstrated that DEPDC1 affected autophagy-dependent glycolysis levels of OS cells by regulating RAS/ERK signaling through TTK.