ArticleBritish journal of cancer2020
A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01791595 (A Cancer Research UK Phase I Trial of AZD3965, a Monocarboxylate Transporter 1 Inhibitor), which is not on this map. Cited by 23 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.
A Cancer Research UK Phase I Trial of AZD3965, a Monocarboxylate Transporter 1 Inhibitor (MCT1) in Patients With Advanced Cancer
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- In Vivo Anticancer Activity of AZD3965: A Systematic Review.Molecules (Basel, Switzerland) · 2021Pooled it
- Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.Cell communication and signaling : CCS · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- [Research progress on protein lactylation modification in malignant tumors].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Review
- Lactate and lactylation: molecular insights into histone and non-histone lactylation in tumor progression, tumor immune microenvironment, and therapeutic strategies.Biomarker research · 2025Review
- Deciphering enemy tactics - the narrow path to an optimal anti-cancer strategy targeting the Warburg effect.Pharmacological reports : PR · 2025Review
- Review
- Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.Molecular oncology · 2025Article
- Lactate Metabolism and Lactylation Modification: New Opportunities and Challenges in Cardiovascular Disease.MedComm · 2025Review
- Metabolic Reprogramming in Melanoma: An Epigenetic Point of View.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers.Cold Spring Harbor perspectives in medicine · 2024Review
- The Significance of Microenvironmental and Circulating Lactate in Breast Cancer.International journal of molecular sciences · 2023Review
- A Phase I Dose-escalation Study of AZD3965, an Oral Monocarboxylate Transporter 1 Inhibitor, in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Targeting cancer lactate metabolism with synergistic combinations of synthetic catalysts and monocarboxylate transporter inhibitors.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer.Biomolecules · 2022Review
- TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.Journal of hematology & oncology · 2022Review
- Influence of the Metabolism on Myeloid Cell Functions in Cancers: Clinical Perspectives.Cells · 2022Review
- Clinical development of metabolic inhibitors for oncology.The Journal of clinical investigation · 2022Review
- Construction of a Lactate-Related Prognostic Signature for Predicting Prognosis, Tumor Microenvironment, and Immune Response in Kidney Renal Clear Cell Carcinoma.Frontiers in immunology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A 47-year-old man with metastatic melanoma presented with refractory hyperlactaemic acidosis following the first dose of the mono-carboxylase transporter 1 inhibitor AZD3965 within a "first time in man" clinical trial. The mechanism of the agent and the temporal relationship suggested that this event was potentially drug related and recruitment was suspended. However, urinary metabolomics showed extensive abnormalities even prior to drug administration, leading to investigations for an underlying metabolic disorder. The lack of clinical symptoms from the elevated lactate and low blood glucose suggested a diagnosis of "hyper-Warburgism", where the high tumour burden was associated with extensive glucose uptake and lactate efflux from malignant cells, and the subsequent impact on blood biochemistry. This was supported by an FDG-PET scan showing extensive glucose uptake in numerous metastases and lack of uptake in the brain. A review of the literature showed 16 case reports of "hyper-Warburgism" in non-haematological malignancies, none of them with melanoma, with most associated with a poor outcome. The patient was treated symptomatically, but died 2 months later. The development of AZD3965 continues with the exclusion of patients with elevated plasma lactate at screening added to the protocol as a safety measure.Trial identification number ClinicalTrials.Gov. NCT01791595.
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.