ArticleCancer discovery2023
Discovery of Targets for Immune-Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor Alpha.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 37 citations in OpenAlex.
- A novel PAAoptosis-inducing ERRα-targeting compound for combating hematopoietic and solid cancers.Cell death discovery · 2026Article
- ERRγ impedes neuroendocrine prostate cancer development.Genes & development · 2026Article
- Reference-guided computational framework identifies microenvironment metabolic subtypes and targets using pan-cancer single-cell datasets.Genome medicine · 2025Article
- Ailanthone induces triple-negative breast cancer cells death involving the inhibition of OTUB1-mediated ERRα deubiquitylation.Journal of advanced research · 2025Article
- Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer.Journal for immunotherapy of cancer · 2025Article
- Facts and Hopes: Toward the Next Quantum Leap in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Spatially resolved C1QCCell discovery · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Emerging artificial intelligence-driven precision therapies in tumor drug resistance: recent advances, opportunities, and challenges.Molecular cancer · 2025Review
- Prognostic assessment of cervical cancer based on biomarkers: the interaction of ERRα and immune microenvironment.Virology journal · 2025Article
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
- Deciphering ERR family genes as prognostic and immunological biomarkers through pan-cancer analysis with validation in gallbladder cancer.Frontiers in oncology · 2025Article
- The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.Cancer research · 2024Article
- Targeting metabolism to enhance immunotherapy within tumor microenvironment.Acta pharmacologica Sinica · 2024Review
- Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma.Experimental & molecular medicine · 2024Article
- Robust identification of perturbed cell types in single-cell RNA-seq data.Nature communications · 2024Article
- Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks.Oncogene · 2024Article
- Editorial: Multi-omics studies on aging and age-related diseases.Frontiers in cell and developmental biology · 2024Article
- Repurposing of Antidiarrheal Loperamide for Treating Melanoma by Inducing Cell Apoptosis and Cell Metastasis SuppressionCurrent cancer drug targets · 2024Article
- Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
32 authors at 8 institutions in 3 countries.
Funding
Abstract
Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell-specific regulators that simultaneously modulate tumor immunity and another oncogenic pathway and then used it to identify 38 candidate immune-metabolic regulators. We show the tumor activities of these regulators stratify patients with melanoma by their response to anti-PD-1 using machine learning and deep neural approaches, which improve the predictive power of current biomarkers. The topmost identified regulator, ESRRA, is activated in immunotherapy-resistant tumors. Its inhibition killed tumors by suppressing energy metabolism and activating two immune mechanisms: (i) cytokine induction, causing proinflammatory macrophage polarization, and (ii) antigen-presentation stimulation, recruiting CD8+ T cells into tumors. We also demonstrate a wide utility of BipotentR by applying it to angiogenesis and growth suppressor evasion pathways. BipotentR (http://bipotentr.dfci.harvard.edu/) provides a resource for evaluating patient response and discovering drug targets that act simultaneously through multiple mechanisms. SIGNIFICANCE: BipotentR presents resources for evaluating patient response and identifying targets for drugs that can kill tumors through multiple mechanisms concurrently. Inhibition of the topmost candidate target killed tumors by suppressing energy metabolism and effects on two immune mechanisms. This article is highlighted in the In This Issue feature, p. 517.
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What Socratic 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 Socratic graph.