ERBB4 (erb-b2 receptor tyrosine kinase 4)

These findings establish NRG4 as a metastasis suppressor in obesity-associated breast cancer by inhibiting the ERBB4-YAP1 pathway and down-regulating matrix metalloproteinases. Our study highlights the therapeutic potential of targeting NRG4-ERBB4 signaling to mitigate obesity-driven breast cancer progression.

LINC01515 upregulates ERBB4 expression in GC by sponging miR-325-3p, thereby promoting tumor growth. These findings highlight the LINC01515/miR-325-3p/ERBB4 axis as a potential therapeutic target for GC.

P1, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2028 | Trial primary completion date: Oct 2025 --> Oct 2028

Trastuzumab (TRZ), a humanized monoclonal antibody targeting ErbB2/HER2, is used for the therapy of HER2-positive breast cancer...We found that the up-regulated NRG1 compensates for insulin deficiency to maintain systolic function in the early stage of diabetic cardiomyopathy. This review aims to discuss the physiological roles of NRG1-ErbB2 signaling in the cardiovascular system, the cardioprotective effects of NRG1 and its clinical applications, and the molecular mechanisms of TRZ-induced cardiotoxicity through the blockade of the NRG1-ErbB2 signaling pathway.

In vivo, CAF-conditioned medium promoted tumor growth, while NRG1 knockdown reduced this effect. Our findings suggest that CAF-secreted NRG1 is closely associated with TNBC progression and may represent a potential biomarker and therapeutic target, although further validation is needed to establish causality.

These findings advance the concept of 'differentiation therapy' as a promising intervention to reduce phenotypic plasticity and malignancy in pHGG ecosystems. While these are early in vitro findings, the potential ability to steer and control glioma cells toward stable, less malignant fates offers promising translational potential for patient-centered targeted therapies.

Our findings indicate that, based on alteration patterns, survivability, differential gene and protein level expressions, the genes ERBB3, ERBB4, HLA-B, AKT1, GNAS, FGFR4, PIK3R3 and AXIN2 emerge as primary risk factors in TNBC. These genes, associated with specific subtypes, are potential markers and should be the focus of further studies, paving the way for personalized anticancer treatment strategies for TNBC patients.

More detailed analyses of the most potent mutations, S303F, E452K, and L798R, showed that they are activating, can co-operate with other ERBB receptors and are sensitive to clinically available second-generation pan-ERBB inhibitors neratinib, afatinib, and dacomitinib. Furthermore, the S303F mutation, together with a previously identified activating ERBB4 mutation, E715K, promoted resistance to third-generation EGFR inhibitor osimertinib in EGFR-mutant lung cancer model in vitro and in vivo. Together, these results are expected to facilitate clinical interpretation of the most recurrent cancer-associated ERBB4 mutations. The findings provide rationale for testing the efficacy of clinically used pan-ERBB inhibitors in patients harboring driver ERBB4 mutations both in the treatment-naïve setting, and upon development of resistance to targeted agents.

Under hypoxic conditions, miR-652-5p promoter hypermethylation promotes GBM malignancy via the SDC1/TGFβ2/pERBB4 axis in a HIF2α-dependent manner. Understanding this mechanism may lead to the development of epigenetic treatments and personalized medical approaches to improve patient outcomes.

This comprehensive single-cell analysis increases our understanding of AT2 cells molecular and dynamics of metastatic lung cancer. In summary, single-cell RNA profiling of LUAD offers valuable prognostic insights based on AT2 cell types and identifies potential biomarkers for therapeutic responses, aiding the future development of LUAD treatment strategies.

Critically, we observed an inverse correlation between neuroimmune gene expression and inflammation markers in advanced HCC, suggesting that neuroimmune suppression may facilitate immune evasion. These findings highlight the neuroimmunome as a potential biomarker and therapeutic target in hepatitis and its complications, reinforcing the role of neuroimmune crosstalk in liver disease progression.

The NRG-1/ErbBs signaling pathway mitigates p53 activation and, through this mechanism, promotes DNA repair, facilitates cell cycle progression, inhibits apoptosis, and reduces inflammation. Collectively, these effects enhance cardiomyocyte proliferation and confer cardioprotection against radiation-induced injury.