ReviewCureus2025
The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.
Review in Cureus, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Immunohistochemical Expression of Endoplasmic Reticulum Stress Markers and their Association With Clinicopathological Characteristics and Survival Outcomes in Endometrial Cancer.Cancer diagnosis & prognosisArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unfolded protein response (UPR) mediated by IRE1/XBP1, PERK/eIF2α/ATF4, and ATF6/GRP78 governs tumor adaptation to hypoxia, nutrient deprivation, and therapy stress. In gynecologic malignancies (ovarian, endometrial, cervical), persistent endoplasmic reticulum (ER)-stress signaling underlies proliferation, invasion, immune evasion, and treatment resistance but also creates druggable liabilities. We conducted a narrative review of peer-reviewed literature indexed in MEDLINE (PubMed), Embase, Scopus, and Web of Science from inception through 13 September 2025. Search terms combined ER-stress/UPR pathways with gynecologic cancers. Eligible records included recent and high-quality preclinical, translational, and clinical studies, clinical trials, and high-quality reviews focused on UPR biology, biomarkers, or therapeutics. Data were synthesized by disease site and UPR branch. Across tumor types, UPR activation correlates with aggressive phenotypes and poorer outcomes. In epithelial ovarian cancer, GRP78/ATF6/PERK overexpression associates with inferior survival and chemoresistance, supporting their utility as biomarkers and therapeutic targets. Endometrial cancer demonstrates UPR gene-signature stratification of prognosis and immune infiltration, suggesting risk-adapted strategies. Cervical cancer leverages PERK/IRE1 signaling for therapy tolerance and dormancy. The tumor-immune interface is UPR-sensitive: CHOP and myeloid IRE1α signaling can dampen antitumor immunity, providing a rationale to pair UPR modulation with immunotherapy. Therapeutically, IRE1 RNase inhibitors (e.g., MKC-8866, B-I09), PERK/EIF2AK3 pathway modulators, protein-disulfide isomerase inhibition, and agents that trigger irrecoverable ER stress show preclinical efficacy, including synergy with platinum, poly (ADP-ribose) polymerase (PARP) inhibitors, HDAC6 blockers, and PD-1 inhibitors. Early clinical efforts investigating ER-stress-modulating combinations in platinum-resistant ovarian cancer highlight translational promise but remain preliminary. Thus, ER-stress/UPR signaling is a convergent, targetable axis in gynecologic cancers. Priorities include validating UPR-based prognostic signatures, defining context-specific vulnerabilities (e.g., genotype-informed IRE1/XBP1 dependence), and executing biomarker-driven clinical trials that combine UPR-targeted agents with standard chemotherapy, PARP inhibition, and immunotherapy to overcome resistance and improve patient outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.