ArticleNature communications2018
Systems analysis of intracellular pH vulnerabilities for cancer therapy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers, 3 of them syntheses that pooled it.
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
193 citing papers in PubMed, 3 syntheses or guidelines pooled it, 408 citations in OpenAlex.
- Melatonin in glioblastoma therapy: clinical promise and mechanistic insights from bench to bedside.Neurosurgical review · 2026Pooled it
- Hydrated proton complexes supplementation for tumor microenvironment reprogramming: a bioenergetic strategy targeting the Warburg effect and mitochondrial dysfunction.Frontiers in oncology · 2025Pooled it
- Systematic Review of Cancer Targeting by Nanoparticles Revealed a Global Association between Accumulation in Tumors and Spleen.International journal of molecular sciences · 2021Pooled it
- Activatable NIR-II photoacoustic probes for cancer imaging and imaging-guided therapy.Bioactive materials · 2026Review
- Article
- Hyperpolarization of PyridineAngewandte Chemie (International ed. in English) · 2026Article
- The anion channel GPR89 is a tumor-specific dependency in breast cancer.Nature communications · 2026Article
- Combinatorial Treatment with Chlorogenic Acid and Cinnamaldehyde Disrupts Intracellular pH and Metabolic Transport in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- FLASH radiotherapy: physico-chemical considerations on ionisation tracks, radical reactions, and the role of oxygen.Radiation oncology (London, England) · 2026Review
- Vimentin remodeling in response to oxidants and electrophiles is modulated by pH.Science advances · 2026Article
- Beyond a Metabolite: Lactylation as a Pivotal Regulator of Colorectal Cancer Pathogenesis and Treatment Resistance.Journal of biochemical and molecular toxicology · 2026Review
- Synergistic Probe Combining Lysosome Anchoring and Tumor Defense System Targeting for Precise Tumor Visualization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.Cell communication and signaling : CCS · 2026Review
- Acidosis-associated gene signature defines novel subtypes and dual-target therapeutic candidates in breast cancer.Journal of translational medicine · 2026Article
- Digital Microneedles for Multiplexed Transdermal Sensing via Fluorescent QR Codes.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Photocaged Chloroquine Derivatives for the Light-Dependent Inhibition of Autophagy in Cancer Stem Cells.ACS chemical biology · 2026Article
- The cellular landscape of i-motifs: genomic insights, methodological challenges, and the road ahead.Genome biology · 2026Review
- DUSP29 does not regulate melanoma-myoblast interactions in a skeletal muscle co-culture model.Scientific reports · 2026Article
- Metabolic plasticity of sphingolipids governs cancer cell fitness in acidic tumor ecosystems.bioRxiv : the preprint server for biology · 2026Article
- Stimuli-Responsive Supramolecular Biomaterials for Cancer Theranostics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
133 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 7 institutions in 3 countries.
Funding
Abstract
A reverse pH gradient is a hallmark of cancer metabolism, manifested by extracellular acidosis and intracellular alkalization. While consequences of extracellular acidosis are known, the roles of intracellular alkalization are incompletely understood. By reconstructing and integrating enzymatic pH-dependent activity profiles into cell-specific genome-scale metabolic models, we develop a computational methodology that explores how intracellular pH (pHi) can modulate metabolism. We show that in silico, alkaline pHi maximizes cancer cell proliferation coupled to increased glycolysis and adaptation to hypoxia (i.e., the Warburg effect), whereas acidic pHi disables these adaptations and compromises tumor cell growth. We then systematically identify metabolic targets (GAPDH and GPI) with predicted amplified anti-cancer effects at acidic pHi, forming a novel therapeutic strategy. Experimental testing of this strategy in breast cancer cells reveals that it is particularly effective against aggressive phenotypes. Hence, this study suggests essential roles of pHi in cancer metabolism and provides a conceptual and computational framework for exploring pHi roles in other biomedical domains.
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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.