IRS2 (Insulin receptor substrate 2)

The integrated analysis of longitudinal WES data from primary tumors and matched PDXs enabled the identification of a core set of conserved, potentially deleterious mutations. The four prioritized mutations (PTPRK, PIK3CB, LRP1B, and IGF2R) provide new insights into the genetic landscape of gastric cancer and represent promising candidates for the development of targeted therapeutic strategies.

These siRNAs reduced IRS2 expression in tumor and stromal cells without causing hyperglycemia, resulting in reduced tumor growth that was associated with decreased vascularization and alterations in macrophage polarization and the expression of EMT proteins. This work demonstrates that siRNAs can be delivered to neoplastic and specific stromal populations in mammary tumors and that they can effectively and specifically silence a driver of aggressive breast cancer.

On the basis of our findings, STAT3 and ITGB6 were statistically associated with lymph node metastasis. Thus, we hypothesised that their increased expression can lead to the migration of cancer cells, resulting in lymph node metastasis and affecting overall survival. Further understanding of the signalling pathways mediating STAT3 and ITGB6 may help identify valid therapeutic targets for OSCC patients.

IRS2 amplification represents a recurrent but non-universal molecular alteration enriched in a subset of colorectal cancer brain metastases, with mechanistic links to β-catenin signaling and mitochondrial metabolism. Preclinical inhibition of IRS2/IRS1-2 demonstrates translational promise, positioning IRS2 as a context-dependent vulnerability and potential therapeutic target in selected CRC brain-metastatic tumors.

Our findings suggest that miR-let-7a and IRS2 are promising targets for the development of immunotherapy for gastric cancer. Moreover, establishing systems for the endogenous delivery of miR-let-7a may provide innovative strategies to impede gastric cancer progression.

Single-cell analysis provides additional functional evidence supporting ~45% of these genes, and experimental validation confirms oncogenic roles for RHPN2, IRS2, and TXN. Our findings elucidate key TF-gene regulatory networks and uncover novel CRC risk genes.

This study demonstrated that 1 year of treatment with biosimilar infliximab GP1111 was safe regardless of treatment history. The rate of serious infections was comparable to originator tumor necrosis factor inhibitors.

In conclusion, this proteomics study achieved to date the most comprehensive understanding of PR-regulated molecular networks that are strongly anti-proliferative and proapoptotic with pivotal involvement of mitochondria. PR agonists warrant evaluation for the treatment of breast cancer with high PR expression.

Moreover, two clinical trials of neoadjuvant AR inhibition prior to radical prostatectomy showed greater increases in AKT activation in the T:E fusion-positive versus -negative tumors. These findings indicate that AKT activation may mitigate the efficacy of AR-targeted therapy in T:E fusion PCa and that these patients may most benefit from combination therapy targeting AR and AKT.

Tunicamycin and thapsigargin were used for the induction of ER stress. Conclusion. Our findings provide evidence that hypoxic regulation of IRS2 gene expression is modified by inducers of ER stress and hydrocortisone, but differently in normal astrocytes and glioblastoma cells and that the combined effect of hypoxia with ER stress and hydrocortisone greatly enhanced this gene expression in both cell types, especially in the glioblastoma cells.

Moreover, ATRA improved insulin-stimulated glucose uptake in adipocytes rendered insulin-resistant by coculture (p < 0.01), an effect associated with the restoration of glucose transporter 4 (GLUT4) and insulin receptor substrate-2 (IRS-2) expression. These findings suggest that ATRA effectively mitigates inflammation and insulin resistance arising from adipocyte-macrophage interactions, highlighting its potential as a therapeutic agent for obesity-related metabolic disorders.

Conversely, AR and IRS2 inhibitors like EPI-7170 and NT157 negatively affected PCa progression. These results underscore HIC1's potential as a therapeutic target in PCa, offering new insights into its role in cancer biology and treatment.