NEK1 (NIMA Related Kinase 1)

Mutations including NEK11p.E347V (31/31), NEK9p.R429H (23/31), NEK10p.L513S (15/31), NEK4p.P136A (7/31), NEK5p.K255Q (6/31) and NEK1 p.E650G (5/31) were found to be recurring mutations and can be validated further in large-scale studies for biomarker applicability. Collectively, these findings suggest NEK mutations as candidate drivers of OSCC pathogenesis, underscoring their potential as prognostic biomarkers and therapeutic targets, particularly in tobacco-associated disease.

These findings indicate that METTL1-mediated m7G modification is vital for OSCC proliferation, with NEK1 identified as a significant downstream target. In conclusion, METTL1 stands out as a potential prognostic marker and therapeutic target in OSCC, highlighting the need for further exploration of its molecular mechanisms and clinical implications.

In vivo, low-dose prexasertib exhibits immune-modulatory effects and synergizes safely with immune checkpoint blockade at subtherapeutic doses. Our findings establish reduced-dose CHK1 inhibition as a strategy to amplify immunotherapy efficacy while circumventing systemic toxicity, providing a translatable framework for optimizing therapeutic windows in clinical oncology.

Our findings highlight the importance of MTFR1 in modulating mitochondrial dynamics and its potential impact on colon cancer cell survival under metabolic stress. These results suggest that MTFR1 serine 119 could be a key regulator of colon cancer cell metabolism and a potential therapeutic target for enhancing cancer cell response to metabolic challenges.

Specifically, an NEK2 inhibitor, T-1101 tosylate, is currently undergoing clinical trials. This review will focus on the gene expression and functional roles of NEKs in GI cancers, as well as the progress in developing NEK inhibitors.

In due course, this results first in a pro-survival quiescence and then adaptation to ADT and CRPC progression. This constitutes a novel liability for PCa that we have targeted for several years and novel approaches.

(2) The enhanced degradation of (cytoplasmic) YAP is increased by J54 counteracting its Enzalutamide-induced accumulation...(5) While xenografts of LNCaP cells show rapid regression following treatment with ARSI+J54, in the VCaP model, driven by the TMPRSS2-ERG oncogenic translocation, tumors initially respond well to the combination but subsequently recur, despite the continuous suppression of pNek1-T141 and pYAP-Y407. This suggests an alternative parallel pathway for CRPC progression for VCaP tumors in the long term, which may be separate from the observed ENZ-driven YAP deregulation, although clearly some YAP gene targets like PD-L1, that are found to accumulate following prolonged ENZ treatment, are still suppressed by the concomitant addition of J54.

Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied...Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.

These results indicate that NEK family members are significantly differentially expressed in ccRCC, and a significant correlation exists between the NEK family and prognosis and immune infiltration. NEK family members may act as therapeutic targets and prognostic indicators in ccRCC.

Our results suggest that NEK9 in particular has the potential to be used as a diagnostic and prognostic biomarker of STAD development and progression and an immune target for treatment of the disease. These findings expand our understanding of the biological functions of the NEK family members in STAD.

We validated the above findings using qRT-PCR and the protein expression of NEKs in EAC cell lines using Western blotting and in primary EAC tissues using immunohistochemistry and immunofluorescence. Our data suggest that frequent upregulation of NEK2, NEK3, and NEK7 may be important in EAC.

In addition, antisense oligonucleotides and RNA gene therapies have successfully been employed against other diseases, such as childhood-onset spinal muscular atrophy (SMA), which could also give hope to ALS patients. Therefore, an effective gene and biomarker panel should be generated for potentially "at risk" individuals to provide timely interventions and better treatment outcomes for ALS patients as soon as possible.