ArticleThe Journal of clinical investigation2018
Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 258 citations in OpenAlex.
- New Hope for Pancreatic Ductal Adenocarcinoma Treatment Targeting Endoplasmic Reticulum Stress Response: A Systematic Review.International journal of molecular sciences · 2018Pooled it
- The Unfolded Protein Response as a Modulator of Cancer-Immune Cell Communication in the Tumour Microenvironment.Journal of cellular and molecular medicine · 2026Review
- The anion channel GPR89 is a tumor-specific dependency in breast cancer.Nature communications · 2026Article
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting the IRE1α-XBP1 signaling axis impairs tumor growth and promotes myogenic differentiation in rhabdomyosarcoma.Communications biology · 2026Article
- Targeting the IRE1α-XBP1 signaling axis impairs tumor growth and promotes myogenic differentiation in rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Metformin triggers apoptosis via endoplasmic reticulum stress in HER2-positive breast cancer cell lines.Experimental and therapeutic medicine · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Intercellular Horizontal Transfer of TXNDC5 mRNA via Extracellular Vesicles Contributes to Tumor-Associated Macrophage-Mediated Prostate Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.International journal of molecular sciences · 2026Article
- From stress to homeostasis: Mass spectrometry-based insights into the unfolded protein response (UPR) and proteostasis.Advances in biological regulation · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- MYC affects mitochondrial function in IgA nephropathy by promoting the degradation of MFN1 through HRD1.Immunologic research · 2025Article
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
- HERPUD1 mediates palmitic acid-induced UPR sustaining TNBC aggressiveness and is destabilized by CK2 pharmacological inhibition.Cell death & disease · 2025Article
- XBP1s Mediates Cross-resistance to Combination Treatment of CDK4/6 Inhibitors plus Endocrine Therapy in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Leukocyte-intrinsic ER stress responses contribute to chemotherapy-induced peripheral neuropathy.Science translational medicine · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 11 institutions in 4 countries.
Funding
Abstract
The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms. We found that MYC directly controls IRE1 transcription by binding to its promoter and enhancer. Furthermore, MYC forms a transcriptional complex with XBP1, a target of IRE1, and enhances its transcriptional activity. Importantly, we demonstrate that XBP1 is a synthetic lethal partner of MYC. Silencing of XBP1 selectively blocked the growth of MYC-hyperactivated cells. Pharmacological inhibition of IRE1 RNase activity with small molecule inhibitor 8866 selectively restrained the MYC-overexpressing tumor growth in vivo in a cohort of preclinical patient-derived xenograft models and genetically engineered mouse models. Strikingly, 8866 substantially enhanced the efficacy of docetaxel chemotherapy, resulting in rapid regression of MYC-overexpressing tumors. Collectively, these data establish the synthetic lethal interaction of the IRE1/XBP1 pathway with MYC hyperactivation and provide a potential therapy for MYC-driven human breast cancers.
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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.