CHD1 (Chromodomain Helicase DNA Binding Protein 1)

Notably, this CHD1-deficient epigenetic state confers resistance to NSD2 inhibition. These findings highlight a previously unrecognized role in tumor resistance for CHD1 in modulating HMEs that may influence lineage plasticity as well as suggest new avenues for personalized therapeutic strategies targeting CHD1-specific epigenetic vulnerabilities.

Immune checkpoint blockade is more effective in a syngeneic mouse model of melanoma deficient in Chd1 and Map3k7 and is associated with elevated intra-tumoral CD8+ T cell numbers and activation. CHD1 and MAP3K7 are recurrently mutated in cancer, and reduced expression in tumors correlates with response to immune checkpoint inhibitors in patients, nominating these genes as potential biomarkers of immunotherapy response.

Our study demonstrates that CHD1L is markedly upregulated in prostate cancer and contributes to tumor progression. Pharmacological inhibition of CHD1L with the selective inhibitor OTI-611 significantly suppresses proliferation, migration, and invasion, while inducing apoptosis in vitro and in vivo. Mechanistically, these effects are mediated through activation of the FOXO3-PUMA axis, as FOXO3 suppression abrogates OTI-611-induced apoptosis. Moreover, OTI-611 exhibits strong synergy with docetaxel, enhancing apoptotic cell death and providing a potential strategy to improve therapeutic efficacy in prostate cancer.

This study identifies a novel signaling cascade whereby TMZ-resistant GBM secretes COL6A1 to activate an IKZF1-UBD axis in ECs, disrupting blood vessel integrity and facilitating MDM infiltration. Our findings delineate the pivotal mechanism by which tumor cells engage ECs to drive MDM infiltration - a linchpin part of the positive-feedback loop that couples TMZ resistance to MDM influx. Targeting IKZF1 with LEN represents a promising strategy for restoring endothelial barrier function, reducing MDM infiltration, and enhancing chemosensitivity in GBM.

Moreover, CHD1 knockdown or pharmacological inhibition of IL7R synergistically enhanced platinum sensitivity, suggesting promising combination therapies specifically targeting the R175G mutation. The findings revealed that p53 mutations at the same residue exhibited distinct functional properties and relied on unique cofactors, offering valuable insights for precision therapy in OC.

Among these components, MLL mutations frequently co-occur with CHD1 mutations in various cancers, suggesting a shared pathway in cancer development. These findings underscore the importance of chromatin remodeler condensation as a regulatory hub in various cellular processes and tumor suppression.

Furthermore, SETD3 mediates methylation of CHD1 to enhance H3K4me3 epigenetic marks and promote transcriptional activation of TNF-NFκB pathway genes. Collectively, our findings establish CHD1 as a new substrate for SETD3 and reveal a mechanism by which SETD3-mediated dimethylation of CHD1 at K209 promotes tumor progression.

While SENP7 can indirectly affect DNA methylation through the deSUMOylation of the chromatin repressor KAP1, UTF1 and VENTX are two genes involved in embryonic development not previously implicated in epigenetic regulation. Our findings shed new light on the processes involved in cPCDH methylation that may underlie associations with neurological disease.

CHCHD1 expression correlated with Th2 cell infiltration (R = 0.57, p = 0.025) and programmed cell death 1 expression (p = 0.027). CHCHD1 promotes EMT and immune evasion in HCC via TGF-β1 signaling, implicating it as a promising biomarker and therapeutic target.

Further analysis indicated that high CHD1 expression in tumors correlated with improved overall survival in nivolumab-treated patients but not in those receiving everolimus. However, these results enhance our understanding of the genetic predisposition to trAEs and provide a significant step toward safer and more effective cancer treatment strategies. This study was registered on the University Hospital Medical Information Network (UMIN) in Japan on August 20, 2019 (protocol ID: UMIN000037739).

This axis sustains the tumor-initiating and regenerative capacity of LUAD progenitor cells. By illuminating the role of L1CAM and PCP signaling in the generation of SOX2 + LUAD progenitors, our findings identify potential new targets to treat metastatic cancer.

Incorporation of PGAs from ctDNA into a CG model improved OS prediction by nearly 30% over a clinical model. This model can classify patients into risk groups and is useful for selecting patients in future mCRPC trials.