{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:19:40Z","timestamp":1793755180825,"version":"4.6.1"},"reference-count":161,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNRS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Cancer cells are associated with high glycolytic activity, which results in acidification of the tumor microenvironment. The occurrence of this stressful condition fosters tumor aggressiveness, with the outcome of invasiveness and metastasis that are linked to a poor clinical prognosis. Acidosis can be both the cause or consequence of alterations in the functions and expressions of transporters involved in intracellular acidity regulation. This review aims to explore the origin of acidity in cancer cells and the various mechanisms existing in tumors to resist, survive, or thrive in the acidic environment. It highlights the difficulties in measuring the intracellular pH evolution that impedes our understanding of the many regulatory and feedback mechanisms. It finally presents the consequences of acidity on tumor development as well as the friend or foe role of acidity in therapy.<\/jats:p>","DOI":"10.3390\/biology13040225","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T06:33:16Z","timestamp":1711693996000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["On the Importance of Acidity in Cancer Cells and Therapy"],"prefix":"10.3390","volume":"13","author":[{"given":"Alaa","family":"Tafech","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-0425","authenticated-orcid":false,"given":"Ang\u00e9lique","family":"St\u00e9phanou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","first-page":"6449","article-title":"Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review","volume":"49","author":"Vaupel","year":"1989","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/bjc.1988.210","article-title":"pH distributions in spontaneous and isotransplanted rat tumours","volume":"58","author":"Kallinowski","year":"1988","journal-title":"British J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/j.1582-4934.2009.00994.x","article-title":"Tumour hypoxia induces a metabolic shift causing acidosis: A common feature in cancer","volume":"14","author":"Chiche","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrc3038","article-title":"Otto Warburg\u2019s contributions to current concepts of cancer metabolism","volume":"11","author":"Koppenol","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1001\/jama.1926.02680200071042","article-title":"Ueber den Stoffwechsel der Tumoren: Arbeiten aus dem Kaiser Wilhelm-Institut f\u00fcr Biologie, Berlin-Dahlem","volume":"87","author":"Warburg","year":"1926","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/35025220","article-title":"Angiogenesis in cancer and other diseases","volume":"407","author":"Carmeliet","year":"2000","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrc905","article-title":"Clinical translation of angiogenesis inhibitors","volume":"2","author":"Kerbel","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","unstructured":"Serres, S., O\u2019Brien, E.R., and Sibson, N.R. (2014). Tumor Microenvironment and Cellular Stress. Advances in Experimental Medicine and Biology, Springer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.stem.2018.11.011","article-title":"Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance","volume":"24","author":"Gupta","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_11","first-page":"2366","article-title":"Paclitaxel induces apoptosis via protein kinase A- and p38 mitogen-activated protein-dependent inhibition of the Na+\/H+ exchanger (NHE) NHE isoform 1 in human breast cancer cells","volume":"9","author":"Reshkin","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bedessem, B., and St\u00e9phanou, A. (2014). Role of Compartmentalization on HiF-1a Degradation Dynamics during Changing Oxygen Conditions: A Computational Approach. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110495"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1152\/physrev.1981.61.2.296","article-title":"Intracellular pH","volume":"61","author":"Roos","year":"1981","journal-title":"Physiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj2500001","article-title":"Regulation of intracellular pH in eukaryotic cells","volume":"250","author":"Madshus","year":"1988","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1021\/bi00314a038","article-title":"Characterization of potent sodium\/proton exchange inhibitors from the amiloride series in A431 cells","volume":"23","author":"Zhuang","year":"1984","journal-title":"Biochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Druzhkova, I., Shirmanova, M., Lukina, M., Dudenkova, V., Sergeeva, T., Belousov, V., Lukyanov, S., and Zagaynova, E. (2015, January 21\u201325). Registration of intracellular pH in cancer cells with genetically encoded ratiometric sensor. Proceedings of the European Conference on Biomedical Optics 2015, Munich, Germany.","DOI":"10.1364\/ECBO.2015.953710"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/j.bbagen.2015.05.001","article-title":"Intracellular pH imaging in cancer cells in vitro and tumors in vivo using the new genetically encoded sensor SypHer2","volume":"1850","author":"Shirmanova","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jmri.10181","article-title":"MRI of the tumor microenvironment","volume":"16","author":"Gillies","year":"2002","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tafech, A., Jacquet, P., Beaujean, C., Fertin, A., Usson, Y., and St\u00e9phanou, A. (2023). Characterization of the Intracellular Acidity Regulation of Brain Tumor Cells and Consequences for Therapeutic Optimization of Temozolomide. Biology, 12.","DOI":"10.3390\/biology12091221"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/sj.bjc.6604111","article-title":"Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype","volume":"98","author":"Barathova","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16400","DOI":"10.1074\/jbc.M901201200","article-title":"Function of a Subunit Isoforms of the V-ATPase in pH Homeostasis and in Vitro Invasion of MDA-MB231 Human Breast Cancer Cells","volume":"284","author":"Hinton","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/jps.10389","article-title":"Molecular Features, Regulation, and Function of Monocarboxylate Transporters: Implications for Drug Delivery","volume":"92","author":"Enerson","year":"2003","journal-title":"J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.2174\/138161210793429841","article-title":"Recent Advances in Structural Studies of the Carbonic Anhydrase Family: The Crystal Structure of Human CA IX and CA XIII","volume":"16","author":"Supuran","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nature04871","article-title":"Hypoxia signalling in cancer and approaches to enforce tumour regression","volume":"441","author":"Dayan","year":"2006","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10482","DOI":"10.1073\/pnas.0403930101","article-title":"Lipid- and mechanosensitivities of sodium\/hydrogen exchangers analyzed by electrical methods","volume":"101","author":"Fuster","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrc1713","article-title":"The role of disturbed pH dynamics and the Na+\/H+ exchanger in metastasis","volume":"5","author":"Cardone","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbcan.2005.06.004","article-title":"The role of pH dynamics and the Na+\/H+ antiporter in the etiopathogenesis and treatment of cancer. Two faces of the same coin\u2014One single nature","volume":"1756","author":"Harguindey","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00424-009-0677-8","article-title":"Protons make tumor cells move like clockwork","volume":"458","author":"Stock","year":"2009","journal-title":"Pfl\u00fcgers Archiv.-Eur. J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1083\/jcb.105.4.1637","article-title":"Structure of the novel membrane-coating material in proton-secreting epithelial cells and identification as an H+ATPase","volume":"105","author":"Brown","year":"1987","journal-title":"J. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1152\/physrev.1989.69.3.765","article-title":"Structure and function of vacuolar class of ATP-driven proton pumps","volume":"69","author":"Forgac","year":"1989","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/j.1749-6632.1992.tb43834.x","article-title":"A Plasma Membrane V-type H+-ATPase May Contribute to Elevated Intracellular pH (pHin) in Some Human Tumor Cells","volume":"671","author":"Gillies","year":"1992","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C1015","DOI":"10.1152\/ajpcell.1993.265.4.C1015","article-title":"Vacuolar-type H(+)-ATPases are functionally expressed in plasma membranes of human tumor cells","volume":"265","author":"Lynch","year":"1993","journal-title":"Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/(SICI)1097-4652(199807)176:1<196::AID-JCP21>3.0.CO;2-4","article-title":"Distinct regulation of pHin and [Ca2+]in in human melanoma cells with different metastatic potential","volume":"176","author":"Martinez","year":"1998","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"C1443","DOI":"10.1152\/ajpcell.00407.2003","article-title":"Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: Distribution and functional activity","volume":"286","author":"Sennoune","year":"2004","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_35","first-page":"3930","article-title":"Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/j.1349-7006.2011.01908.x","article-title":"Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells","volume":"102","author":"Izumi","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1158\/0008-5472.CAN-06-3184","article-title":"Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231","volume":"67","author":"Gallagher","year":"2007","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/00001756-200103260-00030","article-title":"Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues","volume":"12","author":"Froberg","year":"2001","journal-title":"Neuroreport"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cbpa.2010.06.161","article-title":"Perspectives on carbonic anhydrase","volume":"157","author":"Gilmour","year":"2010","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/14756360410001689540","article-title":"Review Article","volume":"19","author":"Pastorekova","year":"2004","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/path.1120","article-title":"Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c-erbB2","volume":"197","author":"Parkkila","year":"2002","journal-title":"J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0002-9440(10)64038-2","article-title":"Expression of Hypoxia-Inducible Cell-Surface Transmembrane Carbonic Anhydrases in Human Cancer","volume":"158","author":"Ivanov","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.febslet.2004.10.043","article-title":"Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH","volume":"577","author":"Casini","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1158\/0008-5472.CAN-08-2470","article-title":"Hypoxia-Inducible Carbonic Anhydrase IX and XII Promote Tumor Cell Growth by Counteracting Acidosis through the Regulation of the Intracellular pH","volume":"69","author":"Chiche","year":"2008","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/jcp.22400","article-title":"pH control mechanisms of tumor survival and growth","volume":"226","author":"Parks","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/jcp.24346","article-title":"Hypoxia promotes tumor cell survival in acidic conditions by preserving ATP levels","volume":"228","author":"Parks","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20299","DOI":"10.1074\/jbc.M109.006478","article-title":"The Role of Carbonic Anhydrase 9 in Regulating Extracellular and Intracellular pH in Three-dimensional Tumor Cell Growths","volume":"284","author":"Swietach","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.1038\/sj.onc.1207764","article-title":"Strict regulation of CAIXG250\/MN by HIF-1\u03b1 in clear cell renal cell carcinoma","volume":"23","author":"Grabmaier","year":"2004","journal-title":"Oncogene"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12596","DOI":"10.1073\/pnas.95.21.12596","article-title":"Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes","volume":"95","author":"Ivanov","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16233","DOI":"10.1073\/pnas.0908301106","article-title":"Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX","volume":"106","author":"Alterio","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/07357900802653464","article-title":"Expression and Activity of Carbonic Anhydrase IX Is Associated With Metabolic Dysfunction in MDA-MB-231 Breast Cancer Cells","volume":"27","author":"Li","year":"2009","journal-title":"Cancer Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1007\/BF02389687","article-title":"Immunohistochemical demonstration of human carbonic anhydrase isoenzyme II in brain tumours","volume":"27","author":"Parkkila","year":"1995","journal-title":"Histochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nordfors, K., Haapasalo, J., Korja, M., Niemel\u00e4, A., Laine, J., Parkkila, A.K., Pastorekova, S., Pastorek, J., Waheed, A., and Sly, W.S. (2010). The tumour-associated carbonic anhydrases CA II, CA IX and CA XII in a group of medulloblastomas and supratentorial primitive neuroectodermal tumours: An association of CA IX with poor prognosis. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-148"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/modpathol.2009.189","article-title":"Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors","volume":"23","author":"Parkkila","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1113\/jphysiol.2005.102590","article-title":"Carbonic anhydrase gene expression in CA II-deficient (Car2\u2212\/\u2212) and CA IX-deficient (Car9\u2212\/\u2212) mice","volume":"571","author":"Pan","year":"2006","journal-title":"J. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrc3579","article-title":"Disrupting proton dynamics and energy metabolism for cancer therapy","volume":"13","author":"Parks","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_57","first-page":"2127","article-title":"Proton Transport Inhibitors as Potentially Selective Anticancer Drugs","volume":"29","author":"Harguindey","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10555-007-9064-0","article-title":"Regulation of tumor pH and the role of carbonic anhydrase 9","volume":"26","author":"Swietach","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_59","first-page":"1497","article-title":"Cytotoxicity of compounds that interfere with the regulation of intracellular pH: A potential new class of anticancer drugs","volume":"47","author":"Rotin","year":"1987","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/bjc.1996.254","article-title":"The chronic administration of drugs that inhibit the regulation of intracellular pH: In vitro and anti-tumour effects","volume":"73","author":"Yamagata","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1023\/A:1018446104071","article-title":"Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism","volume":"15","author":"Montcourrier","year":"1997","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Grillon, E., Farion, R., Fablet, K., Waard, M.D., Tse, C.M., Donowitz, M., R\u00e9my, C., and Coles, J.A. (2011). The Spatial Organization of Proton and Lactate Transport in a Rat Brain Tumor. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017416"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"26991","DOI":"10.1074\/jbc.M311838200","article-title":"CD44 Interaction with Na+-H+ Exchanger (NHE1) Creates Acidic Microenvironments Leading to Hyaluronidase-2 and Cathepsin B Activation and Breast Tumor Cell Invasion","volume":"279","author":"Bourguignon","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_64","first-page":"6517","article-title":"Pericellular pH affects distribution and secretion of cathepsin B in malignant cells","volume":"54","author":"Rozhin","year":"1994","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.canlet.2010.03.001","article-title":"Inhibition of Na+\/H+ exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility","volume":"295","author":"Yang","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10938","DOI":"10.1074\/jbc.M411313200","article-title":"Acidic Extracellular pH Induces Matrix Metalloproteinase-9 Expression in Mouse Metastatic Melanoma Cells through the Phospholipase D-Mitogen-activated Protein Kinase Signaling","volume":"280","author":"Kato","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1158\/0008-5472.CAN-12-2796","article-title":"Acidity Generated by the Tumor Microenvironment Drives Local Invasion","volume":"73","author":"Estrella","year":"2013","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Robey, I.F., and Nesbit, L.A. (2013). Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/485196"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/cdd.2010.150","article-title":"Acidic stress promotes a glioma stem cell phenotype","volume":"18","author":"Hjelmeland","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.yexcr.2011.11.014","article-title":"Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment","volume":"318","author":"Rattigan","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","article-title":"Inhibitory effect of tumor cell\u2013derived lactic acid on human T cells","volume":"109","author":"Fischer","year":"2007","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1158\/0008-5472.CAN-11-1272","article-title":"Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-Infiltrating T Lymphocytes","volume":"72","author":"Calcinotto","year":"2012","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0014-4827(73)90561-2","article-title":"Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes","volume":"77","author":"Roos","year":"1973","journal-title":"Exp. Cell Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/261702a0","article-title":"Aerobic glycolysis during lymphocyte proliferation","volume":"261","author":"Wang","year":"1976","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/bj1100373","article-title":"Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes","volume":"110","author":"Hedeskov","year":"1968","journal-title":"Biochem. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1051\/medsci\/20132911020","article-title":"L\u2019effet Warburg","volume":"29","author":"Razungles","year":"2013","journal-title":"Med. Sci. (Paris)"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate","volume":"21","author":"Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1089\/ars.2016.6750","article-title":"Heterogeneity in Cancer Metabolism: New Concepts in an Old Field","volume":"26","author":"Gentric","year":"2017","journal-title":"Antioxidants Redox Signal."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"40621","DOI":"10.18632\/oncotarget.9746","article-title":"Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jacquet, P., and St\u00e9phanou, A. (2023). A reduced model of cell metabolism to revisit the glycolysis-OXPHOS relationship in the deregulated tumor microenvironment. J. Theor. Biol., 562.","DOI":"10.1016\/j.jtbi.2023.111434"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.1038\/srep04927","article-title":"Beyond Warburg effect\u2014Dual metabolic nature of cancer cells","volume":"4","author":"Xie","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Jacquet, P., and St\u00e9phanou, A. (2022). Searching for the Metabolic Signature of Cancer: A Review from Warburg\u2019s Time to Now. Biomolecules, 12.","DOI":"10.3390\/biom12101412"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0027-5107(92)90235-T","article-title":"Clastogenicity of low pH to various cultured mammalian cells","volume":"268","author":"Morita","year":"1992","journal-title":"Fundam. Mol. Mech. Mutagen."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.1073\/pnas.0935978100","article-title":"Acidic pH induces topoisomerase II-mediated DNA damage","volume":"100","author":"Xiao","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","first-page":"3910","article-title":"p53-dependent induction of WAF1 by a low-pH culture condition in human glioblastoma cells","volume":"57","author":"Ohtsubo","year":"1997","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1038\/sj.onc.1202660","article-title":"An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: Implications for clonal selection during colorectal carcinogenesis","volume":"18","author":"Williams","year":"1999","journal-title":"Oncogene"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"44645","DOI":"10.1074\/jbc.M308099200","article-title":"Na-H Exchange-dependent Increase in Intracellular pH Times G2\/M Entry and Transition","volume":"278","author":"Putney","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Smallbone, K., Maini, P.K., and Gatenby, R.A. (2010). Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity. BMC Biol. Direct, 5.","DOI":"10.1186\/1745-6150-5-22"},{"key":"ref_92","unstructured":"Caldwell, P.C. (1956). International Review of Cytology, Elsevier."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1113\/jphysiol.1974.sp010516","article-title":"Intracellular pH of snail neurones measured with a new pH-sensitive glass micro-electrode","volume":"238","author":"Thomas","year":"1974","journal-title":"J. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/BF00583762","article-title":"Intracellular pH regulation in papillary muscle cells from streptozotocin diabetic rats: An ion-sensitive microelectrode study","volume":"412","author":"Chesnais","year":"1988","journal-title":"Pfl\u00fcgers Archiv.-Eur. J. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-4157(83)90013-8","article-title":"Effects of insulin upon ion transport","volume":"737","author":"Moore","year":"1983","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Biomembr."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/262224a0","article-title":"Microelectrode measurement of the intracellular pH of mammalian heart cells","volume":"262","author":"Ellis","year":"1976","journal-title":"Nature"},{"key":"ref_97","unstructured":"Zeuthen, T. (1980). Current Topics in Membranes and Transport, Elsevier."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF00584198","article-title":"Intracellular pH and surface pH in skeletal and cardiac muscle measured with a double-barrelled pH microelectrode","volume":"386","year":"1980","journal-title":"Pfl\u00fcgers Archiv.-Eur. J. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1748-1716.1983.tb07255.x","article-title":"A new design of double-barrelled microelectrodes for intracellular pH-measurement in vivo","volume":"118","author":"Hagberg","year":"1983","journal-title":"Acta Physiol. Scand."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1113\/jphysiol.1977.sp011838","article-title":"Micro-electrode measurement of the intracellular pH and buffering power of mouse soleus muscle fibres","volume":"267","author":"Claire","year":"1977","journal-title":"J. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1083\/jcb.86.3.885","article-title":"Intracellular pH in single motile cells","volume":"86","author":"Heiple","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7276","DOI":"10.1016\/S0021-9258(19)43389-9","article-title":"Determination of Intracellular pH by 31P Magnetic Resonance","volume":"248","author":"Moon","year":"1973","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0022-2828(79)90434-6","article-title":"31P nuclear magnetic resonance measurement of cardiac pH in perfused guinea-pig hearts","volume":"11","author":"Salhany","year":"1979","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0006-291X(88)90560-8","article-title":"31P NMR measurements of myocardial pH invivo","volume":"151","author":"Brindle","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/nbm.1940060407","article-title":"Extracellular volume and transsarcolemmal proton movement during ischemia and reperfusion: A31P NMR spectroscopic study of the isovolumic rat heart","volume":"6","author":"Clarke","year":"1993","journal-title":"NMR Biomed."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/cvr\/cvp396","article-title":"Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: A 13C and 31P magnetic resonance spectroscopy study","volume":"86","author":"Schroeder","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_107","first-page":"I3-14","article-title":"Contribution of tissue acidosis to ischemic injury in the perfused rat heart","volume":"53","author":"Williamson","year":"1976","journal-title":"Circulation"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1113\/jphysiol.1981.sp013892","article-title":"The role of intrarenal pH in regulation of ammoniagenesis: [31P]NMR studies of the isolated perfused rat kidney","volume":"319","author":"Ackerman","year":"1981","journal-title":"J. Physiol."},{"key":"ref_109","unstructured":"Adam, W.R., Koretsky, A.P., and Weiner, M.W. (1985). Contributions to Nephrology, S.Karger AG."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"F904","DOI":"10.1152\/ajprenal.1986.251.5.F904","article-title":"31P-NMR in vivo measurement of renal intracellular pH: Effects of acidosis and K+ depletion in rats","volume":"251","author":"Adam","year":"1986","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"F265","DOI":"10.1152\/ajprenal.1978.235.4.F265","article-title":"Ammonia metabolism","volume":"235","author":"Tannen","year":"1978","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"14409","DOI":"10.1073\/pnas.2332656100","article-title":"Measurement of unidirectional Pi to ATP flux in human visual cortex at 7 T by using 31 P magnetic resonance spectroscopy","volume":"100","author":"Lei","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/mrm.10379","article-title":"In vivo31P magnetic resonance spectroscopy of human brain at 7 T: An initial experience","volume":"49","author":"Lei","year":"2003","journal-title":"Magn. Reson. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0167-7012(97)00031-6","article-title":"Flow cytometry for the intracellular pH measurement of glutamate producing Corynebacterium glutamicum","volume":"29","author":"Leyval","year":"1997","journal-title":"J. Microbiol. Methods"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0168-1656(94)00130-5","article-title":"Measurement of yeast intracellular pH by image processing and the change it undergoes during growth phase","volume":"38","author":"Imai","year":"1995","journal-title":"J. Biotechnol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0304-4165(91)90014-8","article-title":"Continuous measurement of the cytoplasmic pH in Lactococcus lactis with a fluorescent pH indicator","volume":"1115","author":"Molenaar","year":"1991","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1113\/jphysiol.1979.sp013059","article-title":"Intracellular pH and the distribution of weak acids and bases in isolated rat superior cervical ganglia","volume":"297","author":"Brown","year":"1979","journal-title":"J. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0304-4157(81)90004-6","article-title":"pH homesstasis in bacteria","volume":"650","author":"Padan","year":"1981","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Biomembr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1172\/JCI103852","article-title":"Calculation of intracellular pH from the distribution of 5,5-Dimethyl-2,4-Oxazolidinedione (DMO). Application to skeletal muscle of the dog","volume":"38","author":"Waddell","year":"1959","journal-title":"J. Clin. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1172\/JCI113896","article-title":"Intracellular pH during \u201cchemical hypoxia\u201d in cultured rat hepatocytes. Protection by intracellular acidosis against the onset of cell death","volume":"83","author":"Gores","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1128\/jvi.70.10.7049-7055.1996","article-title":"Human immunodeficiency virus infection of T-lymphoblastoid cells reduces intracellular pH","volume":"70","author":"Makutonina","year":"1996","journal-title":"J. Virol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/BF01128970","article-title":"Cell surface effects of human immunodeficiency virus","volume":"8","author":"Garry","year":"1988","journal-title":"Biosci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"5447","DOI":"10.1128\/jvi.70.8.5447-5454.1996","article-title":"Alteration of intracellular potassium and sodium concentrations correlates with induction of cytopathic effects by human immunodeficiency virus","volume":"70","author":"Voss","year":"1996","journal-title":"J. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1208\/ps040421","article-title":"Monitoring intracellular pH changes in response to osmotic stress and membrane transport activity using 5-chloromethylfluorescein","volume":"4","author":"Salvi","year":"2002","journal-title":"AAPS PharmSci"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1073\/pnas.75.7.3327","article-title":"Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents","volume":"75","author":"Ohkuma","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/290527a0","article-title":"A non-disruptive technique for loading calcium buffers and indicators into cells","volume":"290","author":"Tsien","year":"1981","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Tafech, A., Beaujean, C., Usson, Y., and St\u00e9phanou, A. (2023). Generalization of the Ratiometric Method to Extend pH Range Measurements of the BCECF Probe. Biomolecules, 13.","DOI":"10.3390\/biom13030442"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10585-008-9145-7","article-title":"Acid treatment of melanoma cells selects for invasive phenotypes","volume":"25","author":"Moellering","year":"2008","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.semcancer.2008.03.011","article-title":"Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression","volume":"18","author":"Fang","year":"2008","journal-title":"Semin. Cancer Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10555-019-09792-7","article-title":"Causes, consequences, and therapy of tumors acidosis","volume":"38","author":"Pillai","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0003-2697(83)90648-6","article-title":"An electrochemical cell for reduction of biochemicals: Its application to the study of the effect of pH and redox potential on the activity of hydrogenases","volume":"130","year":"1983","journal-title":"Anal. Biochem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"63408","DOI":"10.18632\/oncotarget.11503","article-title":"Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance","volume":"7","author":"Avnet","year":"2016","journal-title":"Oncotarget"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1593\/neo.05697","article-title":"Impact of Extracellular Acidity on the Activity of P-glycoprotein and the Cytotoxicity of Chemotherapeutic Drugs","volume":"8","author":"Thews","year":"2006","journal-title":"Neoplasia"},{"key":"ref_134","first-page":"746025","article-title":"Adverse Cell Culture Conditions Mimicking the Tumor Microenvironment Upregulate ABCG2 to Mediate Multidrug Resistance and a More Malignant Phenotype","volume":"2012","author":"Cheng","year":"2012","journal-title":"ISRN Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1038\/onc.2012.183","article-title":"LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump","volume":"32","author":"Fan","year":"2012","journal-title":"Oncogene"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Visioli, F., Wang, Y., Alam, G.N., Ning, Y., Rados, P.V., N\u00f6r, J.E., and Polverini, P.J. (2014). Glucose-Regulated Protein 78 (Grp78) Confers Chemoresistance to Tumor Endothelial Cells under Acidic Stress. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101053"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.tem.2013.01.006","article-title":"Role of ABC transporters in lipid transport and human disease","volume":"24","author":"Tarling","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.bbcan.2007.05.002","article-title":"Chemotherapy-induced resistance by ATP-binding cassette transporter genes","volume":"1775","author":"Gillet","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Federici, C., Petrucci, F., Caimi, S., Cesolini, A., Logozzi, M., Borghi, M., D\u2019Ilio, S., Lugini, L., Violante, N., and Azzarito, T. (2014). Exosome Release and Low pH Belong to a Framework of Resistance of Human Melanoma Cells to Cisplatin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088193"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.drup.2017.10.003","article-title":"Not only P-glycoprotein: Amplification of the ABCB1- containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins","volume":"32","author":"Genovese","year":"2017","journal-title":"Drug Resist. Updat."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1046\/j.1471-4159.2001.00113.x","article-title":"\u03b2-Amyloid efflux mediated by p-glycoprotein","volume":"76","author":"Lam","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00253-007-1017-6","article-title":"Availability and applications of ATP-binding cassette (ABC) transporter blockers","volume":"76","year":"2007","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_143","unstructured":"Thews, O., Riemann, A., Nowak, M., and Gekle, M. (2014). Advances in Experimental Medicine and Biology, Springer."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00280-011-1598-8","article-title":"Accumulation and distribution of doxorubicin in tumour spheroids: The influence of acidity and expression of P-glycoprotein","volume":"68","author":"Mellor","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"9045","DOI":"10.1021\/bi00197a003","article-title":"NMR and Molecular Modeling Investigation of the Mechanism of Activation of the Antitumor Drug Temozolomide and Its Interaction with DNA","volume":"33","author":"Denny","year":"1994","journal-title":"Biochemistry"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/psp.2014.9","article-title":"Multiscale Design of Cell-Type-Specific Pharmacokinetic\/Pharmacodynamic Models for Personalized Medicine: Application to Temozolomide in Brain Tumors","volume":"3","author":"Ballesta","year":"2014","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1158\/0008-5472.CAN-16-2983","article-title":"Temozolomide in the Era of Precision Medicine","volume":"77","author":"Thomas","year":"2017","journal-title":"Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e00454","DOI":"10.1002\/prp2.454","article-title":"pH as a potential therapeutic target to improve temozolomide antitumor efficacy: A mechanistic modeling study","volume":"7","author":"Ballesta","year":"2019","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.gendis.2016.04.007","article-title":"Temozolomide resistance in glioblastoma multiforme","volume":"3","author":"Lee","year":"2016","journal-title":"Genes Dis."},{"key":"ref_150","first-page":"17","article-title":"Mechanisms of temozolomide resistance in glioblastoma\u2014A comprehensive review","volume":"4","author":"Singh","year":"2020","journal-title":"Cancer Drug Resist."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0163-7258(99)00073-X","article-title":"Resistance mechanisms associated with altered intracellular distribution of anticancer agents","volume":"85","author":"Larsen","year":"2000","journal-title":"Pharmacol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/ijc.20959","article-title":"Na+\/H+ exchanger activity is increased in doxorubicin-resistant human colon cancer cells and its modulation modifies the sensitivity of the cells to doxorubicin","volume":"115","author":"Miraglia","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"7865","DOI":"10.1158\/0008-5472.CAN-07-0353","article-title":"Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells","volume":"67","author":"Rebillard","year":"2007","journal-title":"Cancer Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1756-9966-29-44","article-title":"Proton pump inhibitors as anti vacuolar-ATPases drugs: A novel anticancer strategy","volume":"29","author":"Spugnini","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/ijc.25009","article-title":"pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity","volume":"127","author":"Milito","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/ijc.1418","article-title":"Elevated expression of vacuolar proton pump genes and cellular ph in cisplatin resistance","volume":"93","author":"Murakami","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"36534","DOI":"10.1074\/jbc.M202605200","article-title":"Enhanced Expression of the Human Vacuolar H+-ATPase c subunit Gene (ATP6L) in Response to Anticancer Agents","volume":"277","author":"Torigoe","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-10-2828","article-title":"Lactate Influx through the Endothelial Cell Monocarboxylate Transporter MCT1 Supports an NF-\u03baB\/IL-8 Pathway that Drives Tumor Angiogenesis","volume":"71","author":"Boidot","year":"2011","journal-title":"Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1097\/01.tp.0000287543.91765.41","article-title":"The Specific Monocarboxylate Transporter (MCT1) Inhibitor, AR-C117977, a Novel Immunosuppressant, Prolongs Allograft Survival in the Mouse","volume":"84","author":"Bueno","year":"2007","journal-title":"Transplantation"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1097\/01.tp.0000287541.53389.be","article-title":"The Specific Monocarboxylate Transporter-1 (MCT-1) Inhibitor, AR-C117977, Induces Donor-Specific Suppression, Reducing Acute and Chronic Allograft Rejection in the Rat","volume":"84","author":"Ekberg","year":"2007","journal-title":"Transplantation"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrd3554","article-title":"Interfering with pH regulation in tumours as a therapeutic strategy","volume":"10","author":"Neri","year":"2011","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/4\/225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:20:47Z","timestamp":1760106047000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/4\/225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":161,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["biology13040225"],"URL":"https:\/\/doi.org\/10.3390\/biology13040225","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}