ArticleOncotarget2015
Effective impairment of myeloma cells and their progenitors by blockade of monocarboxylate transportation.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Trial
- The role of lactate on arthritis-associated cells: physiology, pathology, and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels.Cancer & metabolism · 2025Article
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
- Lactate in the tumor microenvironment: A rising star for targeted tumor therapy.Frontiers in nutrition · 2023Review
- Article
- Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma.Experimental hematology & oncology · 2022Review
- An iron chelation-based combinatorial anticancer therapy comprising deferoxamine and a lactate excretion inhibitor inhibits the proliferation of cancer cells.Cancer & metabolism · 2022Article
- Targeting pancreatic cancer with combinatorial treatment of CPI-613 and inhibitors of lactate metabolism.PloS one · 2022Article
- Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies.Frontiers in oncology · 2022Review
- Research Progress on Improving the Efficiency of CDT by Exacerbating Tumor Acidification.International journal of nanomedicine · 2022Review
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
- Drug and Solute Transporters in Mediating Resistance to Novel Therapeutics in Multiple Myeloma.ACS pharmacology & translational science · 2021Review
- Identification of novel anti-tumor therapeutic target via proteomic characterization of ubiquitin receptor ADRM1/Rpn13.Blood cancer journal · 2021Article
- Targeted sensitization of tumor cells for radiation through monocarboxylate transporters 1 and 4 inhibition in vitro.Clinical oral investigations · 2021Article
- Targeting Cancer Metabolism and Current Anti-Cancer Drugs.Advances in experimental medicine and biology · 2021Review
- Role of the Mitochondrial Citrate-malate Shuttle inMetabolites · 2020Article
- Monocarboxylate transporters in cancer.Molecular metabolism · 2020Review
- In Vitro and In Vivo Efficacy of the Monocarboxylate Transporter 1 Inhibitor AR-C155858 in the Murine 4T1 Breast Cancer Tumor Model.The AAPS journal · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells robustly expel lactate produced through enhanced glycolysis via monocarboxylate transporters (MCTs) and maintain alkaline intracellular pH. To develop a novel therapeutic strategy against multiple myeloma (MM), which still remains incurable, we explored the impact of perturbing a metabolism via inhibiting MCTs. All MM cells tested constitutively expressed MCT1 and MCT4, and most expressed MCT2. Lactate export was substantially suppressed to induce death along with lowering intracellular pH in MM cells by blockade of all three MCT molecules with α-cyano-4-hydroxy cinnamate (CHC) or the MCT1 and MCT2 inhibitor AR-C155858 in combination with MCT4 knockdown, although only partially by knockdown of each MCT. CHC lowered intracellular pH and severely curtailed lactate secretion even when combined with metformin, which further lowered intracellular pH and enhanced cytotoxicity. Interestingly, an ambient acidic pH markedly enhanced CHC-mediated cytotoxicity, suggesting preferential targeting of MM cells in acidic MM bone lesions. Furthermore, treatment with CHC suppressed hexokinase II expression and ATP production to reduce side populations and colony formation. Finally, CHC caused downregulation of homing receptor CXCR4 and abrogated SDF-1-induced migration. Targeting tumor metabolism by MCT blockade therefore may become an effective therapeutic option for drug-resistant MM cells with elevated glycolysis.
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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.