ArticleBritish journal of cancer2020
Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds.
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. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Amino acid transporters in hepatocellular carcinoma: Gatekeepers of metabolic reprogramming.Molecular biology reports · 2026Review
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Dynamic evaluation of the glycolytic determinants LDH-A and GLUT-1 enhances prognostic significance and their inhibition affects the growth of mesothelioma spheroids.Molecular metabolism · 2026Article
- Breaking the vicious cycle: Multifunctional nanomaterials targeting Tumor metabolic reprogramming to overcome T cell exhaustion and bone repair failure in bone tumors.Materials today. Bio · 2025Review
- An Overview of Cellular and Molecular Determinants Regulating Chemoresistance in Pleural Mesothelioma.Cancers · 2025Review
- Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives.International journal of biological sciences · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Triggering immunogenic death of cancer cells by nanoparticles overcomes immunotherapy resistance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Targeting the Warburg Effect in Cancer: Where Do We Stand?International journal of molecular sciences · 2024Review
- Deciphering the tumour immune microenvironment cell by cell.Immuno-oncology technology · 2023Review
- Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?International journal of molecular sciences · 2023Review
- Metabolic Effects of New Glucose Transporter (GLUT-1) and Lactate Dehydrogenase-A (LDH-A) Inhibitors against Chemoresistant Malignant Mesothelioma.International journal of molecular sciences · 2023Article
- The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints.International journal of molecular sciences · 2023Review
- Article
- The multiple roles of LDH in cancer.Nature reviews. Clinical oncology · 2022Review
- AdipoRon and Pancreatic Ductal Adenocarcinoma: a future perspective in overcoming chemotherapy-induced resistance?Cancer drug resistance (Alhambra, Calif.) · 2022Article
- The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer.Frontiers in oncology · 2021Review
- A Glimpse in the Future of Malignant Mesothelioma Treatment.Frontiers in pharmacology · 2021Review
- Lactate dehydrogenase A inhibition by small molecular entities: steps in the right direction.Oncoscience · 2020Article
Corrections and comments
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Authors and funding
25 authors at 11 institutions in 6 countries.
Funding
Abstract
backgroundExpression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation.
methodsModulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients.
resultsOverexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine.
conclusionsThis study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors.
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