Regarding treatment, Belinostat, Dabrafenib, and Sorafenib showed higher sensitivity in the low-risk group, whereas Docetaxel demonstrated greater sensitivity in the high-risk category. This study offers a comprehensive analysis of the immune landscape characteristics and potential anticancer drugs in HCC based on PFRGs, providing valuable insights and novel perspectives for the treatment of HCC patients.
To target these epigenetic vulnerabilities, innovative carrier-free nano-epidrugs (siMBD-R NPs) are developed, incorporating first-line doxorubicin (DOX) with siRNA against METTL1 (siMETTL1), FDA-approved HDAC inhibitor belinostat (BEL), and DSPE-PEG2000-cRGD. In vivo studies demonstrate that siMBD-R NPs can significantly potentiate chemosensitivity, achieving an 81.5% relative increase in tumor inhibition, and can activate an immune response. This work highlights the potential benefits of leveraging dual-targeted epigenetic intervention to evoke osteosarcoma chemosensitization.
Finally, belinostat extended in vivo survival only in IDHmut glioma models, not in IDHmut GBM models. Our findings provide a mechanistic rationale for further studies of HDACi in IDHmut glioma patients, as well as the potential use of YAP/TAZ as a biomarker of HDACi sensitivity in cancers.
Three were shown to be beneficial after validation: rucaparib, belinostat and alisertib. The Aurora Kinase A inhibitor alisertib in particular led to an over 4-fold increase in preferential gene correction over gene knock-out in two cell models (HEK293T and Hepa 1-6) at sub-micromolar dosages on the eGFP locus, prompting further validation. On the long term this pathway did show cytotoxicity especially in the HEK293T cells, indicating further mechanistic investigation is needed, but this toxicity was less pronounced in primary hepatocytes.
Although there are many highly selective and potent HDAC inhibitors (such as romidepsin and belinostat), few HAT inhibitors are undergoing clinical trials. Studies have shown that CBP is highly expressed and activated in a variety of different tumors; therefore, its inhibitors have attracted increasing research attention. In this review, we discuss the importance of the structure of CBP in the development of potential inhibitors to provide a reference for the development of new selective CBP inhibitors.
Through this comprehensive pan-cancer analysis, we elucidated novel roles for CD99 in various cancer types, providing important insights for clinical treatment strategies and drug development.
Furthermore, drug sensitivity analysis indicated that high-risk patients were more sensitive to Thapsigargin, Docetaxel, AKT inhibitor VIII, Pyrimethamine, and Epothilone B, while showing higher resistance to drugs such as I-BET-762, PHA-665752, and Belinostat. This study provides a comprehensive analysis of NRGs in BC and establishes reliable ML-based diagnostic and prognostic models. The findings highlight the clinical relevance of NRGs in BC progression, immune regulation, and therapy response, offering potential targets for personalized treatment strategies.
Interestingly, belinostat's anticancer activity was also enhanced by inhibitors of Bcl-xL or Mcl-1 in patient-derived tumor organoids. This study therefore positions belinostat-based strategies as promising therapies for ovarian cancer.