PERK (Pancreatic EIF2-Alpha Kinase)

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.

We discuss the potential of integrating UPR targeting with other therapies, such as immune checkpoint inhibition, highlighting emerging strategies to improve therapeutic efficacy and overcome resistance. These recent insights underscore the importance of UPR as a novel therapeutic target for cancer treatment.

Activation of autophagy by rapamycin counteracted the effects of EIF2AK3 knockdown on both autophagy and PI3K/AKT signaling. Consistently, EIF2AK3 silencing in xenograft models enhanced the therapeutic efficacy of DDP by suppressing autophagy and attenuating PI3K/AKT activation. Collectively, our findings indicate that EIF2AK3 is a critical regulator of hypoxia-triggered autophagy in NSCLC, and targeting EIF2AK3-mediated PI3K/AKT signaling may represent a promising strategy to overcome cisplatin resistance.

TPP1, induced by H. pylori, promoted GC metastasis by enhancing ERS via interaction with GRP78. Targeting the TPP1/ERS axis may offer a novel therapeutic strategy for GC.

There is growing evidence that these hypoxia-induced misfolded proteins contribute to the progression of tumors by causing genomic instability and dysregulating oncogenic signaling. This chapter details how hypoxia regulates protein misfolding, leading to cancer cell adaptation, and outlines relevant therapeutic targets.

Our findings revealed a PERK/MAT2A/PDGFB axis that confers adaptive survival capabilities to CTC clusters in the bloodstream. Targeting this survival signaling pathway represents a promising therapeutic strategy for metastatic cancer.