ArticleNature cancer2022
Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Single-cell RNA sequencing and Mendelian randomization identify context-dependent LIPA-associated classical monocyte states in sepsis and breast cancer.Breast cancer research and treatment · 2026Article
- Cross-Organ Neuroimmunology of Behavior.Annual review of immunology · 2026Review
- In-silico study of machine learning discovers de novo lipogenesis for predicting prognosis and immunotherapy responses in kidney renal clear cell carcinoma.Biology direct · 2026Article
- Targeting LIPA with ERX-41 Induces ER Stress and Inhibits Tumor Progression in Inflammatory Breast Cancer.Biomolecules · 2026Article
- Therapeutic optimization of LIPA targeting to induce endoplasmic reticulum stress and cell death in ovarian cancer.Oncogene · 2026Article
- Liver-specific gene therapy based on self-complementary adeno-associated virus for lysosomal acid lipase deficiency.Frontiers in pharmacology · 2026Article
- Lovastatin Targets LIPA to Induce ER Stress-Mediated Apoptosis in Acute Myeloid Leukemia: A Multi-Omics Study.International journal of general medicine · 2026Article
- Development of a Multigram Synthetic Route to RM-581, an Orally Active Aminosteroid Derivative Against Several Types of Cancers.Molecules (Basel, Switzerland) · 2025Article
- scPRINT: pre-training on 50 million cells allows robust gene network predictions.Nature communications · 2025Article
- Transcriptomic-Based Identification of miR-125a Novel Targets in Human Hepatocarcinoma Cells.Biomolecules · 2025Article
- Strategically engineered Au(I) complexes for orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death.Nature communications · 2024Article
- Self-assembly-integrated tumor targeting and electron transfer programming towards boosting tumor type I photodynamic therapy.Chemical science · 2024Article
- A novel signature integrated endoplasmic reticulum stress and apoptosis related genes to predict prognosis for breast cancer.Heliyon · 2024Article
- Multiomics combined with single-cell analysis shows that mitophagy-related genes could accurately predict the prognosis of patients with clear cell renal cell carcinoma.Translational cancer research · 2024Article
- Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.Cancers · 2024Article
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- In Situ Vaccination with Mitochondria-Targeting Immunogenic Death Inducer Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Development and validation of an endoplasmic reticulum stress-related molecular prognostic model for breast cancer.Frontiers in oncology · 2023Article
- Comprehensive characterization of endoplasmic reticulum stress in bladder cancer revealing the association with tumor immune microenvironment and prognosis.Frontiers in genetics · 2023Article
- Lysosomal Acid Lipase Deficiency: Genetics, Screening, and Preclinical Study.International journal of molecular sciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
29 authors at 6 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.
Indexed as
Identifiers
What OpenQuestion holds
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.