PERK (Pancreatic EIF2-Alpha Kinase)

This Asn-driven regulatory circuit parallels the ATF4-Asn axis in cancer biology, where stress-induced Asn production supports metabolic adaptation, proliferation, and resistance to therapy. Together, these insights position Asn as a central metabolic signal at the intersection of host stress responses and GAS virulence.

Targeting the ISR with small-molecule inhibitors (PERK or GCN2 inhibitors, ISRIB) or repurposed agents (metformin) demonstrates compelling preclinical efficacy in reversing immunosuppression and synergizing with immune checkpoint inhibitors. Biomarker-driven strategies, including ISR gene signatures and p-eIF2α immunohistochemistry, offer promising avenues for patient stratification. Thus, pharmacological targeting of the ISR represents a strategically viable approach to reprogram the immunosuppressive TME and overcome immunotherapy resistance in breast cancer, warranting urgent clinical investigation.

The autophagy-related signature independently predicts CRC prognosis and guides immunotherapy strategies.

Therefore, the present study aimed to investigate the dose-dependent effects of metformin on ER stress and apoptosis in HER2-positive breast cancer SKBR3 cells. The present findings demonstrated that metformin activates ER stress response and induces apoptosis in HER2-positive breast cancer cells in a dose-dependent manner. This supports the potential of metformin as an adjuvant therapy, though further in vivo studies are needed to evaluate its clinical applicability.

However, neither marker demonstrated independent prognostic value for survival outcomes. Further studies are warranted to clarify the role of ER stress pathways in EC biology and their potential implications for risk stratification and targeted therapy.

PDIA6, driven by KRASG12D, alleviates ICD and promotes immune evasion, functioning as a predictive biomarker to screen ICB-sensitive patients and a therapeutic target to improve ICB efficacy in PDAC with KRAS mutations.

P=N/A, N=90, Not yet recruiting, Jiaxing First Hospital; Jiaxing First Hospital

In conclusion, HgCl2 administration to rats caused testicular tissue damage compared to the other groups, but CHR treatment alleviated this damage. Overall, this demonstrates the potential ameliorative mechanisms of CHR as a possible agent for HgCl2-induced testicular damage.

MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death.

Treatment with small molecule eIF2B activators 2BAct and ISRIB increases oligodendrocyte survival, CNS myelination, and doubled the Jimpy lifespan. These results suggest that ISR modulation could provide therapeutic benefit to PMD patients.

The nomogram constructed by ER score and clinical features showed good predictive performance on LUAD. This study provided new insights into understanding the role of ER stress in LUAD.

The ATF3-PCK2 axis facilitates metabolic reprogramming through enhanced anabolic gluconeogenesis, promoting lung cancer malignant progression under NPs exposure. These findings establish NPs as environmental tumor promoters in lung cancer and elucidate a novel metabolic activation pathway underlying their oncogenic effects, providing mechanistic insights with implications for risk assessment, prevention, and therapeutic intervention.