MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7)

Novel protein degrader small molecules which co-opt DCAF16 to degrade BRD4 as a neosubstrate demonstrated preferential selectivity for SF3B1 mutant cancers and CLL primary patient specimens due to increased DCAF16 protein levels. In turn, this reveals the therapeutic relevance of mutant SF3B1 dysregulation of transcript untranslated regions and uncovers a novel strategy for the treatment of these important neoplasms.

In addition, a specificity analysis of exosome RNA data, including gastric cancer, hepatocellular carcinoma, and breast cancer, demonstrated significant specificity for SCLC. Therefore, the novel biomarker screening strategy integrating nested cross-validation with multiple machine learning algorithms successfully established to offer a potentially valuable protocol for early SCLC diagnosis and other cancers.

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.

Adoptive T cell therapy preferentially eliminates TAK1-deficient clones. These findings establish TAK1 as a tumor-intrinsic immune checkpoint and support TAK1 inhibition as a strategy to enhance cancer immunotherapy.

This process can be reversed by the p38 inhibitor Adezmapimod, further confirming that its apoptosis-inducing effect is dependent on the p38 MAPK pathway. This study not only validates the reliability of patient-derived organoids in personalized drug screening but also uncovers the potential therapeutic value of Toyocamycin for TNBC, providing a novel model and theoretical foundation for the precision treatment of TNBC.

Pharmacological inhibition of TAK1 with Takinib, or genetic deletion of MAP3K7 in autochthonous p48-Cre;TP53 flox/flox ;LSL-KRAS G12D GEMM, enhances intratumoral CD4 + and CD8 + effector T cell infiltration and renders immune checkpoint blockade (ICB) effective...At the molecular level, TAK1 phosphorylates Ephrin Receptor A2 (EphA2) at Serine 897, which in turn phosphorylates RAD51 at Tyrosine 315, a key DNA repair protein involved in homologous recombination. We uncover TAK1 as a critical mediator in maintaining genomic integrity and highlights its potential as a therapeutic target to induce an inflamed TME that sensitizes PDAC to ICB.

In vivo experiments indicated that high DPEP2 levels resulted in fewer lung metastases and less M2 macrophage infiltration. Overall, our studies suggest that DPEP2 might be a promising therapeutic target for highly metastatic p53-loss NSCLC by inhibiting tumor metastasis and M2 macrophage capacity.

STRING analysis identified IKBKB as a central hub in the PPI network, while GO enrichment highlighted immune regulation, apoptosis, and NF-κB signaling. These findings demonstrate that adalimumab modulates NF-κB activity in keratinocytes through coordinated regulation of gene, protein, and miRNA expression, providing mechanistic insight into TNF-α blockade in psoriasis.

Translation will require multicenter validation of the ncRNA biomarkers, early-phase trials testing rational MAPK-mTOR combinations with ncRNA modulation, and jaw-targeted delivery approaches. Claims herein are limited to peer-reviewed, ameloblastoma-relevant evidence.

Our study elucidates a significant association between suppressed necroptosis and adverse prognosis in AML. We highlight the role of NRGs in modulating the immune microenvironment of AML and identify potential therapeutic targets and drugs, providing valuable insights for improving clinical outcomes in AML patients.

Notably, treatment with the Caspase-8 inhibitor Z-IETD-FMK markedly reversed PANoptosis in OSCC cells. This study provides the first evidence that PER2 overexpression suppresses OSCC proliferation by regulating the Caspase-8/RIPK3/ASC complex-mediated PANoptosis, offering a promising therapeutic strategy for OSCC.

Notably, miR-103a-3p was downregulated thousands of times in the sera of RA patients and CIA mice, while the blockade of TNF-α with infliximab greatly recovered its levels in RA patients in sustained remission...Mechanistically, mitogen-activated protein kinase kinase kinase 7 (MAP3K7) and Dickkopf-related protein 1 (DKK1) were identified as the direct targets of miR-103a-3p, by which it exerts the effects on synovial inflammation and cartilage bone destruction. Taken together, miR-103a-3p mediates TNF-triggered synovial inflammation and joint bone destruction via targeting MAP3K7 and DKK1; it thus serves as a candidate target for RA treatment.