R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, Cancer statistics, 2022. CA Cancer J. Clin. 72(1), 7–33 (2022)

Article  PubMed  Google Scholar 

J. Kleeff, M. Korc, M. Apte, C. La Vecchia, C.D. Johnson, A.V. Biankin, R.E. Neale, M. Tempero, D.A. Tuveson, R.H. Hruban et al., Pancreatic cancer. Nat. Rev. Dis. Primers. 2, 16022 (2016)

Article  PubMed  Google Scholar 

L. Jorfeldt, A. Juhlin-Dannfelt, J. Karlsson, Lactate release in relation to tissue lactate in human skeletal muscle during exercise. J. Appl. Physiol. Respir Environ. Exerc. Physiol. 44(3), 350–352 (1978)

CAS  PubMed  Google Scholar 

O. Kandler, Carbohydrate metabolism in lactic acid bacteria. Antonie Van Leeuwenhoek. 49(3), 209–224 (1983)

Article  CAS  PubMed  Google Scholar 

R.A. Gatenby, R.J. Gillies, Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer. 4(11), 891–899 (2004)

Article  CAS  PubMed  Google Scholar 

J. Gu, J. Zhou, Q. Chen, X. Xu, J. Gao, X. Li, Q. Shao, B. Zhou, H. Zhou, S. Wei et al., Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-beta signaling in regulatory T cells. Cell. Rep. 39(12), 110986 (2022)

Article  CAS  PubMed  Google Scholar 

Q. Feng, Z. Liu, X. Yu, T. Huang, J. Chen, J. Wang, J. Wilhelm, S. Li, J. Song, W. Li et al., Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity. Nat. Commun. 13(1), 4981 (2022)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S. Kumagai, S. Koyama, K. Itahashi, T. Tanegashima, Y.T. Lin, Y. Togashi, T. Kamada, T. Irie, G. Okumura, H. Kono et al., Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell. 40(2), 201–218 (2022). e209

Article  CAS  PubMed  Google Scholar 

Y. Qian, A. Galan-Cobo, I. Guijarro, M. Dang, D. Molkentine, A. Poteete, F. Zhang, Q. Wang, J. Wang, E. Parra et al., MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma. Cancer Cell. 41(7), 1363–1380e1367 (2023)

Article  CAS  PubMed  PubMed Central  Google Scholar 

D. Sharma, M. Singh, R. Rani, Role of LDH in tumor glycolysis: regulation of LDHA by small molecules for cancer therapeutics. Semin. Cancer Biol. 87, 184–195 (2022)

Article  CAS  PubMed  Google Scholar 

X. Li, Y. Yang, B. Zhang, X. Lin, X. Fu, Y. An, Y. Zou, J.X. Wang, Z. Wang, T. Yu, Lactate metabolism in human health and disease. Signal. Transduct. Target. Ther. 7(1), 305 (2022)

Article  CAS  PubMed  PubMed Central  Google Scholar 

H. Girgis, O. Masui, N.M. White, A. Scorilas, F. Rotondo, A. Seivwright, M. Gabril, E.R. Filter, A.H. Girgis, G.A. Bjarnason et al., Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma. Mol. Cancer. 13, 101 (2014)

Article  PubMed  PubMed Central  Google Scholar 

A. Comandatore, M. Franczak, R.T. Smolenski, L. Morelli, G.J. Peters, E. Giovannetti, Lactate dehydrogenase and its clinical significance in pancreatic and thoracic cancers. Semin Cancer Biol. 86(Pt 2), 93–100 (2022)

Article  CAS  PubMed  Google Scholar 

B.C. Tripp, K. Smith, J.G. Ferry, Carbonic anhydrase: new insights for an ancient enzyme. J. Biol. Chem. 276(52), 48615–48618 (2001)

Article  CAS  PubMed  Google Scholar 

R.A. Cardone, V. Casavola, S.J. Reshkin, The role of disturbed pH dynamics and the Na+/H + exchanger in metastasis. Nat. Rev. Cancer. 5(10), 786–795 (2005)

Article  CAS  PubMed  Google Scholar 

S. Pastorekova, P.J. Ratcliffe, J. Pastorek, Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia. BJU Int. 101(Suppl 4), 8–15 (2008)

Article  CAS  PubMed  Google Scholar 

V. Alterio, M. Hilvo, A. Di Fiore, C.T. Supuran, P. Pan, S. Parkkila, A. Scaloni, J. Pastorek, S. Pastorekova, C. Pedone et al., Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX. Proc. Natl. Acad. Sci. U S A 106(38), 16233–16238 (2009)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S.H. Lee, D. McIntyre, D. Honess, A. Hulikova, J. Pacheco-Torres, S. Cerdan, P. Swietach, A.L. Harris, J.R. Griffiths, Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo. Br. J. Cancer. 119(5), 622–630 (2018)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S. Ames, J.T. Andring, R. McKenna, H.M. Becker, CAIX forms a transport metabolon with monocarboxylate transporters in human breast cancer cells. Oncogene. 39(8), 1710–1723 (2020)

Article  CAS  PubMed  Google Scholar 

V. Liskova, S. Hudecova, L. Lencesova, F. Iuliano, M. Sirova, K. Ondrias, S. Pastorekova, O. Krizanova, Type 1 Sodium Calcium Exchanger forms a complex with carbonic anhydrase IX and Via Reverse Mode Activity contributes to pH control in hypoxic tumors. Cancers (Basel) 2019, 11(8)

C.T. Supuran, V. Alterio, A. Di Fiore, D.A. K, F. Carta, S.M. Monti, De G. Simone, Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: three for the price of one. Med. Res. Rev. 38(6), 1799–1836 (2018)

Article  PubMed  Google Scholar 

H.M. Becker, Carbonic anhydrase IX and acid transport in cancer. Br. J. Cancer. 122(2), 157–167 (2020)

Article  CAS  PubMed  Google Scholar 

E. Panisova, M. Kery, O. Sedlakova, L. Brisson, M. Debreova, M. Sboarina, P. Sonveaux, S. Pastorekova, E. Svastova, Lactate stimulates CA IX expression in normoxic cancer cells. Oncotarget. 8(44), 77819–77835 (2017)

Article  PubMed  PubMed Central  Google Scholar 

E.C. Cheung, K.H. Vousden, The role of ROS in tumour development and progression. Nat. Rev. Cancer. 22(5), 280–297 (2022)

Article  CAS  PubMed  Google Scholar 

D.I. Brown, K.K. Griendling, Nox proteins in signal transduction. Free Radic Biol. Med. 47(9), 1239–1253 (2009)

Article  CAS  PubMed  PubMed Central  Google Scholar 

Y. Shang, E.J. Huang, Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis. Brain Res. 1647, 65–78 (2016)

Article  CAS  PubMed  PubMed Central  Google Scholar 

R. Tang, J. Xu, W. Wang, Q. Meng, C. Shao, Y. Zhang, Y. Lei, Z. Zhang, Y. Liu, Q. Du et al., Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response. Cell. Rep. Med. 4(10), 101234 (2023)

Article  CAS  PubMed  PubMed Central  Google Scholar 

Z. Tang, C. Li, B. Kang, G. Gao, C. Li, Z. Zhang, GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45(W1), W98–W102 (2017)

Article  CAS  PubMed  PubMed Central  Google Scholar 

P. Apostolova, E.L. Pearce, Lactic acid and lactate: revisiting the physiological roles in the tumor microenvironment. Trends Immunol. 43(12), 969–977 (2022)

Article  CAS  PubMed  PubMed Central  Google Scholar 

S. Jamali, M. Klier, S. Ames, L.F. Barros, R. McKenna, J.W. Deitmer, H.M. Becker, Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function. Sci. Rep. 5, 13605 (2015)

Article  PubMed  PubMed Central  Google Scholar 

K. Bedard, K.H. Krause, The NOX family of ROS-generating NA