KDM5D (Lysine Demethylase 5D)

© 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

This axis is linked to the suppression of malignant progression and invasiveness in male CRC cells. These findings suggest a potential epigenetic mechanism contributing to sex-biased CRC behavior, warranting further validation in larger cohorts and functional studies of catalytic dependency.

Correspondingly, a higher sensitivity to SRA737 was observed in a docetaxel-resistant CRPC cell line with elevated KDM5D, and silencing KDM5D caused resistance to this inhibitor. SIGNIFICANCE STATEMENT: This study demonstrated an important role of an epigenetic regulator KDM5D in regulating CHK1 inhibitor sensitivity via a p38/COX-2-mediated prosurvival pathway in certain castration- or drug-resistant PC cells. Our results indicate that PC cells expressing KDM5D may be more sensitive to targeted inhibition of CHK1 kinase, highlighting the potential predictive value of this gene for CHK1-targeted therapies in PC.

Single-cell RNA sequencing further implicated hub genes in immune microenvironment remodeling. The study systematically delineates the compound-target-disease network underlying CS-induced COPD, providing a theoretical basis for prevention, early diagnosis, and targeted therapy of COPD.

LOY/EDY can be detected in OPMD and promotes malignant progression by altering oncogenic signaling and epithelial cell interactions. LOY/EDY may serve as both a diagnostic biomarker and a therapeutic target, improving clinical management and patient outcomes.

Furthermore, we discuss emerging therapeutic strategies aimed at overcoming treatment resistance by targeting KDM5 demethylases. These insights provide a foundation for the development of innovative therapeutic interventions to enhance the efficacy of existing cancer treatments, offering a transformative approach to improving long-term patient survival and quality of life.

While somatic copy number alterations were universally more common to aggressive tumors, besides shared alterations impacting DDX3Y and USP9Y, African derived tumors were prone to somatic losses associated with KDM5D, PCDH11Y, and RBMY. This much-needed African inclusive study alludes to possible Y chromosome contribution, at least in part, to treatment resistance and worsened mortality rates in African men.

Based on the results of bioinformatics analysis and animal experiments, KDM5D serves as a potential biomarker for the diagnosis and prognosis of TBI. Additionally, research on KDM5D may develop into new serum markers, providing new indicators for further clinical liquid biopsy and aiding in the prevention of both TBI and tumors to a certain extent.

The reduced proportion of NTRK1 fusions in disseminated cases relative to solitary cases suggests that NTRK1 fusions are less efficient than MAP kinase pathway point mutations at driving tumor evolution towards disseminated disease. As NTRK1 fusions are uncommon in other histiocytoses, pan-TRK immunostain may have utility to confirm the diagnosis of xanthogranuloma in a histiocytic lineage tumor and to screen for low-risk xanthogranuloma.

The gene expression of the TILB-related signature was also verified in TILBs from HNSCC using single-cell analysis, revealing that TILB-related marker genes were differentially expressed in different GB cell subsets. This study provides risk assessment and outcome prediction for patients with HNSCC and provides potential targets for immunotherapy of HNSCC.

While KDM5C and KDM5D bind to at least some overlapping genomic sites, gene expression changes induced by KDM5C or KDM5D mutation are apparently unrelated to the direct functions of these proteins at the relevant gene promoters or enhancers. Our findings identify similarities and differences in KDM5C and KDM5D functions, challenging the idea that KDM5D in male cells functions equivalently to the second KDM5C allele in female cells, and implicate an interplay between KDM5C mutation and Y chromosome loss in ccRCC development in men.

Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965).