ArticleMolecular cancer therapeutics2015
Acute Tumor Lactate Perturbations as a Biomarker of Genotoxic Stress: Development of a Biochemical Model.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 20 citations in OpenAlex.
- Comparative predictive value of immunotherapy biomarkers: a systematic review and network meta-analysis.International journal of surgery (London, England) · 2026Article
- Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours.Nature reviews. Cancer · 2024Review
- Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.British journal of cancer · 2023Article
- Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy.International journal of biological sciences · 2023Review
- Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here?Frontiers in oncology · 2022Review
- Development of a rational strategy for integration of lactate dehydrogenase A suppression into therapeutic algorithms for head and neck cancer.British journal of cancer · 2021Article
- Why Concurrent CDDP and Radiotherapy Has Synergistic Antitumor Effects: A Review of In Vitro Experimental and Clinical-Based Studies.International journal of molecular sciences · 2021Review
- Targeting cancer-cell mitochondria and metabolism to improve radiotherapy response.Translational oncology · 2021Review
- Revisiting lactate dynamics in cancer-a metabolic expertise or an alternative attempt to survive?Journal of molecular medicine (Berlin, Germany) · 2020Review
- Article
- Role of metabolism in cancer cell radioresistance and radiosensitization methods.Journal of experimental & clinical cancer research : CR · 2018Review
- High-RiskClinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism.Scientific reports · 2018Article
- Article
- MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival.Molecular cancer therapeutics · 2016Article
- Lactate, a Neglected Factor for Diabetes and Cancer Interaction.Mediators of inflammation · 2016Review
- Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance.Frontiers in immunology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Ionizing radiation is the primary nonsurgical treatment modality for solid tumors. Its effectiveness is impacted by temporal constraints such as fractionation, hypoxia, and development of radioresistant clones. Biomarkers of acute radiation response are essential to developing more effective clinical algorithms. We hypothesized that acute perturbations in tumor lactate levels act as a surrogate marker of radiation response. In vitro experiments were carried out using validated human-derived cell lines from three histologies: anaplastic thyroid carcinoma (ATC), head and neck squamous cell carcinoma (HNSCC), and papillary thyroid carcinoma (PTC). Cellular metabolic activity was measured using standard biochemical assays. In vivo validation was performed using both an orthotopic and a flank derivative of a previously established ATC xenograft murine model. Irradiation of cells and tumors triggered a rapid, dose-dependent, transient decrease in lactate levels that was reversed by free radical scavengers. Acute lactate perturbations following irradiation could identify hypoxic conditions and correlated with hypoxia-induced radioresistance. Mutant TP53 cells and cells in which p53 activity was abrogated (shRNA) demonstrated a blunted lactate response to irradiation, consistent with a radioresistant phenotype. Lactate measurements therefore rapidly detected both induced (i.e., hypoxia) and intrinsic (i.e., mutTP53-driven) radioresistance. We conclude that lactate is a quantitative biomarker of acute genotoxic stress, with a temporal resolution that can inform clinical decision making. Combined with the spatial resolution of newly developed metabolic imaging platforms, this biomarker could lead to the development of truly individualized treatment strategies.
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.