ReviewPhilosophical transactions of the Royal Society of London. Series B, Biological sciences2014
The chemistry, physiology and pathology of pH in cancer.
Review in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis 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
217 citing papers in PubMed, 1 synthesis or guideline pooled it, 533 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- Activatable NIR-II photoacoustic probes for cancer imaging and imaging-guided therapy.Bioactive materials · 2026Review
- Real-Time Detection of Colorectal Cancer Using Topical Application of a pH-Activatable Fluorophore.Molecular diagnosis & therapy · 2026Article
- Rosindol: A fluorogen for the quantitative measurement of reactive oxygen species in living cells.bioRxiv : the preprint server for biology · 2026Article
- On why cancer cells require a great amount of glucose.Quantitative biology (Beijing, China) · 2026Article
- Dual pH- and Concentration-Dependent KJACS Au · 2026Article
- Why Targeting Tumor Acidity Fails: Translational Barriers and Emerging Solutions.International journal of molecular sciences · 2026Review
- Review
- Stacked-overlapped graphdiyne nano-iontronics enabling enhanced monovalent/divalent cation selectivity for single-cell pH detection.National science review · 2026Article
- Advances in the applications of stimulus-responsive nanomedicines for anti-cancer therapy.Nanomedicine (London, England) · 2026Review
- Unveiling Targeted Approaches to Combat Drug Resistance in Cancer Chemotherapy.Current pharmaceutical design · 2026Review
- Article
- Association of alkalization therapy with long-term survival in stage IV or recurrent colorectal cancer: interaction with RAS mutation status.Frontiers in oncology · 2026Article
- Development of ROS-responsive liposomes toward targeted drug delivery.Expert opinion on drug delivery · 2025Review
- Photoacoustic Chemical Imaging of Tumor Microenvironment pH for Prediction of Chemotherapeutic Efficacy in Breast Cancer.Nano letters · 2025Article
- Encapsulation of doxorubicin in magnesium acetate liposomes as a pH-sensitive drug carrier for tumor therapy.iScience · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- Structural Impact of 3-methylcytosine Modification on the Anticodon Stem-loop of a Neuronally-enriched Arginine tRNA.Journal of molecular biology · 2025Article
- Electrochemical Control with High Spatiotemporal Resolutions for Extracellular pH Microenvironment.ACS electrochemistry · 2025Article
- Tumor Niche Influences the Activity and Delivery of Anticancer Drugs: Pharmacology Meets Chemistry.Pharmaceuticals (Basel, Switzerland) · 2025Review
157 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid-base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H(+)-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H(+)-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H(+)/H(+)-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H(+)/H(+)-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors.
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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.