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Hypoxic microenvironment in cancer: role in metabolic reprogramming
Open accessAbstract
Hypoxia, a defining hallmark of solid tumors, arises from structurally and functionally abnormal vasculature, rapid cellular proliferation, and impaired perfusion, resulting in chronic and cycling oxygen deprivation within the tumor massThe hypoxic tumor microenvironment orchestrates extensive molecular reprogramming primarily through stabilization and activation of hypoxia-inducible factors (HIF-1α and HIF-2α), which regulate broad transcriptional networks governing metabolism, angiogenesis, stemness, invasion, and immune modulation. Under low oxygen tension, tumor cells shift toward aerobic glycolysis, enhance glutamine utilization, promote lipid synthesis and storage, suppress mitochondrial oxidative phosphorylation, and fine-tune redox balance through coordinated regulation of ROS-generating and antioxidant systems. These adaptations not only sustain proliferation and survival under metabolic stress but also facilitate epithelial–mesenchymal transition, extracellular matrix remodeling, and metastatic dissemination. Beyond malignant cells, hypoxia reprograms stromal compartments—including cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages, and myeloid-derived suppressor cells—thereby establishing a metabolically cooperative, angiogenic, and profoundly immunosuppressive microenvironment. Hypoxia-induced acidosis, lactate accumulation, and HIF-driven cytokine signaling further impair cytotoxic T-cell and NK-cell activity, contributing to immune escape and resistance to radiotherapy, chemotherapy, and immunotherapy. Emerging evidence from single-cell multi-omics, spatial transcriptomics, metabolic imaging, and early-phase clinical trials targeting HIF signaling, angiogenic pathways, and metabolic enzymes has uncovered actionable vulnerabilities in hypoxia-driven malignancies. This review synthesizes the mechanistic foundations of hypoxia-induced metabolic reprogramming, its role in tumor progression and therapeutic resistance, and discusses innovative strategies aimed at exploiting hypoxia-associated metabolic dependencies to advance precision oncology.
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“As tumors grow beyond the reach of blood vessels, hypoxia leads to the stabilization of hypoxia-inducible factor 1α (HIF-1α), which then induces the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis [54].”
From Overcoming Resistance to Anti-EGFR Therapies: Mechanisms of Cetuximab and Panitumumab Resistance and Emerging Combination Strategies (2026) · cites this paper as [54]
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Cites
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
The Warburg Effect: How Does it Benefit Cancer Cells?
Liberti, M. V., & Locasale, J. W. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.001 · Cited by 5,150
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
Functional Polarization of Tumour-Associated Macrophages by Tumour-Derived Lactic Acid
Colegio, O. R., Chu, N.-Q., Szabo, A. L., Chu, T., Rhebergen, A. M., Jairam, V., Cyrus, N., Brokowski, C. E., Eisenbarth, S. C., Phillips, G. M., et al. (2014) · Nature · doi:10.1038/nature13490 · Cited by 3,046
Mao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy
Thomlinson, R. H., & Gray, L. H. (1955) · British Journal of Cancer · doi:10.1038/bjc.1955.55 · Cited by 2,228
Noman, M. Z., Desantis, G., Janji, B., Hasmim, M., Karray, S., Dessen, P., Bronte, V., & Chouaib, S. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131916 · Cited by 2,166
Tumor angiogenesis: causes, consequences, challenges and opportunities
Lugano, R., Ramachandran, M., & Dimberg, A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03351-7 · Cited by 2,149
The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy
Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015) · Hypoxia · doi:10.2147/hp.s93413 · Cited by 2,066 · cited 2×
“Paradoxically, while angiogenesis is initiated to alleviate hypoxia, the resulting vasculature frequently fails to resolve oxygen de fi ciency, thereby creating a vicious cycle of persistent hypoxia and continued HIF activation (19, 165).”
Role of hypoxia in cancer therapy by regulating the tumor microenvironment
Jing, X., Yang, F., Shao, C., Wei, K., Xie, M., Shen, H., & Shu, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1089-9 · Cited by 2,054
LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells
Brand, A., Singer, K., Koehl, G. E., Kolitzus, M., Schoenhammer, G., Thiel, A., Matos, C., Bruss, C., Klobuch, S., Peter, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.011 · Cited by 2,039
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001
Inhibitory effect of tumor cell-derived lactic acid on human T cells
Fischer, K., Hoffmann, P., Voelkl, S., Meidenbauer, N., Ammer, J., Edinger, M., Gottfried, E., Schwarz, S., Rothe, G., Hoves, S., et al. (2007) · Blood · doi:10.1182/blood-2006-07-035972 · Cited by 1,946
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., Sirven, P., Magagna, I., Fuhrmann, L., Bernard, C., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.011 · Cited by 1,705 · cited 1×
“Notably, iCAFs were enriched in immune-regulatory genes and were shown to express immune checkpoint molecules including PD-L1, contributing to T-cell dysfunction and immune exclusion (145).”
Lipid Droplets and Cellular Lipid Metabolism
Walther, T. C., & Farese, R. V. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061009-102430 · Cited by 1,701
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Hypoxia-Inducible Factor-1 (HIF-1)
Ke, Q., & Costa, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.027029 · Cited by 1,690
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612
Role of PFKFB3-Driven Glycolysis in Vessel Sprouting
Bock, K. D., Γεωργιάδου, Μ., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., Quaegebeur, A., Ghesquière, B., Cauwenberghs, S., Eelen, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.037 · Cited by 1,591
Bonnet, S., Archer, S. L., Allalunis‐Turner, J., Haromy, A., Beaulieu, C., Thompson, R. B., Lee, C. T., Lopaschuk, G. D., Puttagunta, L., Bonnet, S. B., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.10.020 · Cited by 1,552
Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy
Semenza, G. L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.01.005 · Cited by 1,514
Angiogenic signaling pathways and anti-angiogenic therapy for cancer
Liu, Z., Chen, H., Zheng, L., Sun, L., & Shi, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01460-1 · Cited by 1,486
The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma
Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A. K., Frank, P. G., Casimiro, M. C., Wang, C., Fortina, P., Addya, S., et al. (2009) · Cell Cycle · doi:10.4161/cc.8.23.10238 · Cited by 1,391
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
Watson, M. J., Vignali, P., Mullett, S. J., Overacre-Delgoffe, A. E., Peralta, R. M., Grebinoski, S., Menk, A. V., Rittenhouse, N., DePeaux, K., Whetstone, R. D., et al. (2021) · Nature · doi:10.1038/s41586-020-03045-2 · Cited by 1,319
Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments
Angelin, A., Gil‐de‐Gómez, L., Dahiya, S., Jiao, J., Guo, L., Levine, M. H., Wang, Z., Quinn, W. J., Kopinski, P. K., Wang, L., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.018 · Cited by 1,304
α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming
Liu, P.-S., Wang, H., Li, X., Chao, T., Teav, T., Christen, S., Di Conza, G., Cheng, W.-C., Chou, C.-H., Vavakova, M., et al. (2017) · Nature Immunology · doi:10.1038/ni.3796 · Cited by 1,264
Hypoxia-Induced Angiogenesis: Good and Evil
Krock, B. L., Skuli, N., & Simon, M. C. (2011) · Genes & Cancer · doi:10.1177/1947601911423654 · Cited by 1,236
Targeting lactate metabolism for cancer therapeutics
Doherty, J. R., & Cleveland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69741 · Cited by 1,195
Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone, R. D., Zhao, L., Englert, J. M., Sun, I.-M., Oh, M.-H., Sun, I.-H., Arwood, M. L., Bettencourt, I. A., Patel, C. H., Wen, J., et al. (2019) · Science · doi:10.1126/science.aav2588 · Cited by 1,169 · cited 1×
“Glutamine blockade impairs tumor cell metabolism while simultaneously promoting oxidative metabolism and effector function in CD8 + T cells (88).”
Reactive Oxygen Species in Cancer: Current Findings and Future Directions
Nakamura, H., & Takada, K. (2021) · Cancer Science · doi:10.1111/cas.15068 · Cited by 1,027
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021
Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology
Kierans, S. J., & Taylor, C. T. (2021) · The Journal of Physiology · doi:10.1113/jp280572 · Cited by 1,015
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885
Guzy, R. D., & Schumacker, P. T. (2006) · Experimental Physiology · doi:10.1113/expphysiol.2006.033506 · Cited by 881
Scharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R. E., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.009 · Cited by 848
Husain, Z., Huang, Y., Seth, P., & Sukhatme, V. P. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202702 · Cited by 827
Lu, J., Tan, M., & Cai, Q. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.04.001 · Cited by 822
Transcriptional regulation by hypoxia inducible factors
Dengler, V. L., Galbraith, M. D., & Espinosa, J. M. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.838205 · Cited by 816
Glutamine Metabolism in Cancer: Understanding the Heterogeneity
Cluntun, A. A., Lukey, M. J., Cerione, R. A., & Locasale, J. W. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.01.005 · Cited by 796
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787
Regulation of glut1 mRNA by Hypoxia-inducible Factor-1
Chen, C., Pore, N., Behrooz, A., Ismail‐Beigi, F., & Maity, A. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010144200 · Cited by 769
Metabolic Modulation of Glioblastoma with Dichloroacetate
Michelakis, E. D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E. B., Maguire, C., Gammer, T.-L., Mackey, J. R., Fulton, D. S., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000677 · Cited by 744
Tumor-derived lactic acid modulates dendritic cell activation and antigen expression
Gottfried, E., Kunz-Schughart, L. A., Ebner, S., Mueller-Klieser, W., Hoves, S., Andreesen, R., Mackensen, A., & Kreutz, M. (2006) · Blood · doi:10.1182/blood-2005-05-1795 · Cited by 729
Hypoxia and Metabolic Adaptation of Cancer Cells
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.50 · Cited by 724 · cited 2×
“This pathway not only supports membrane lipid synthesis essential for cell proliferation but also generates NADPH, a crucial reducing equivalent that fuels antioxidant defenses and anabolic reactions (91, 92).”
Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
Jonasch, E., Donskov, F., Iliopoulos, O., Rathmell, W. K., Narayan, V. K., Maughan, B. L., Oudard, S., Else, T., Maranchie, J. K., Welsh, S. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103425 · Cited by 714 · cited 1×
“Phase II studies in advanced ccRCC have reported durable disease control with a favorable safety pro fi le (191, 192), FDA in 2021 approved belzutifan for patients with VHL-associated RCC (193).”
Targeting renal cell carcinoma with a HIF-2 antagonist
Chen, W., Hill, H., Christie, A., Kim, M. S., Holloman, E., Pavia-Jimenez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., et al. (2016) · Nature · doi:10.1038/nature19796 · Cited by 709
Emami Nejad, A., Najafgholian, S., Rostami, A., Sistani, A., Shojaeifar, S., Esparvarinha, M., Nedaeinia, R., Haghjooy Javanmard, S., Taherian, M., Ahmadlou, M., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-020-01719-5 · Cited by 693
Yang, C., Ko, B., Hensley, C. T., Jiang, L., Wasti, A. T., Kim, J., Sudderth, J., Calvaruso, M. A., Lumata, L., Mitsche, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.025 · Cited by 679
Bensaad, K., Favaro, E., Lewis, C. A., Peck, B., Lord, S., Collins, J. M., Pinnick, K. E., Wigfield, S., Buffa, F. M., Li, J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.056 · Cited by 667
Metabolites and the Tumour Microenvironment: From Cellular Mechanisms to Systemic Metabolism
Elia, I., & Haigis, M. C. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00317-z · Cited by 651
NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications
Ju, H., Lin, J., Tian, T., Xie, D., & Xu, R. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00326-0 · Cited by 607
Zimna, A., & Kurpisz, M. (2015) · BioMed Research International · doi:10.1155/2015/549412 · Cited by 604
Graham, K., & Unger, E. C. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s140462 · Cited by 594
PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response
Abu Shelbayeh, O., Arroum, T., Morris, S., & Busch, K. B. (2023) · Antioxidants · doi:10.3390/antiox12051075 · Cited by 552
Lactate and lactylation in cancer
Chen, J., Huang, Z., Chen, Y., Tian, H., Chai, P., Shen, Y., Yao, Y., Xu, S., Ge, S., & Jia, R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02082-x · Cited by 545
Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target
Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115703 · Cited by 541
Sonveaux, P., Copetti, T., De Saedeleer, C. J., Végran, F., Verrax, J., Kennedy, K. M., Moon, E. J., Dhup, S., Danhier, P., Frérart, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033418 · Cited by 536
Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation
Brown, J. M. (1979) · British Journal of Radiology · doi:10.1259/0007-1285-52-620-650 · Cited by 527
Hypoxia-Modified Cancer Cell Metabolism
Tameemi, W. A., Dale, T. P., Al-Jumaily, R. M. K., & Forsyth, N. R. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00004 · Cited by 524
The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond
Pastoreková, S., & Gillies, R. J. (2019) · Cancer and Metastasis Reviews · doi:10.1007/s10555-019-09799-0 · Cited by 473
HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
Du, W., Zhang, L., Brett-Morris, A., Aguila, B., Kerner, J., Hoppel, C. L., Puchowicz, M., Serra, D., Herrero, L., Rini, B. I., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01965-8 · Cited by 468
Oh, M.-H., Sun, I.-H., Zhao, L., Leone, R. D., Sun, I.-M., Xu, W., Collins, S. L., Tam, A. J., Blosser, R. L., Patel, C. H., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci131859 · Cited by 456
Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity
Feng, Q., Liu, Z., Yu, X., Huang, T., Chen, J., Wang, J., Wilhelm, J., Li, S., Song, J., Li, W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32521-8 · Cited by 430
Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment
Pérez‐Tomás, R., & Pérez-Guillén, I. (2020) · Cancers · doi:10.3390/cancers12113244 · Cited by 418
The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF
Ghalehbandi, S., Yüzügülen, J., Pranjol, M. Z. I., & Pourgholami, M. H. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175586 · Cited by 416
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer
Bae, T., Hallis, S. P., & Kwak, M. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01180-8 · Cited by 410
Understanding and targeting resistance mechanisms in cancer
Lei, Z., Qin, T., Teng, Q., Wurpel, J. N. D., Zeng, L., Pan, Y., & Chen, Z. (2023) · MedComm · doi:10.1002/mco2.265 · Cited by 406
Courtney, K. D., Infante, J. R., Lam, E. T., Figlin, R. A., Rini, B. I., Brugarolas, J., Zojwalla, N. J., Lowe, A. M., Wang, K., Wallace, E. M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.2627 · Cited by 393
Edwards, D. N., Ngwa, V. M., Raybuck, A. L., Wang, S., Hwang, Y., Kim, L. C., Cho, S. H., Paik, Y., Wang, Q., Zhang, S., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci140100 · Cited by 389
Hypoxia and Aggressive Tumor Phenotype: Implications for Therapy and Prognosis
Vaupel, P. W. (2008) · The Oncologist · doi:10.1634/theoncologist.13-s3-21 · Cited by 383
Rischin, D., Peters, L. J., O'Sullivan, B., Giralt, J., Fisher, R., Yuen, K., Trotti, A., Bernier, J., Bourhis, J., Ringash, J., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4449 · Cited by 380
Vascular Permeability and Drug Delivery in Cancers
Azzi, S., Hebda, J. K., & Gavard, J. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00211 · Cited by 379
Lipid Droplets in Cancer: Guardians of Fat in a Stressful World
Petan, T., Jovičić, E. J., & Jusović, M. (2018) · Molecules · doi:10.3390/molecules23081941 · Cited by 379
Makino, Y., Kanopka, A., Wilson, W. J., Tanaka, H., & Poellinger, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200328200 · Cited by 376
Huang, D., Li, T., Li, X., Zhang, L., Sun, L., He, X., Zhong, X., Jia, D., Song, L., Semenza, G. L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.028 · Cited by 352
Nath, A., Li, I., Roberts, L. R., & Chan, C. (2015) · Scientific Reports · doi:10.1038/srep14752 · Cited by 347
Hypoxia-inducible factor 2 regulates hepatic lipid metabolism
Rankin, E. B., Rha, J., Selak, M. A., Unger, T. L., Keith, B., Liu, Q., & Haase, V. H. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00200-09 · Cited by 338
A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma
Wallace, E. M., Rizzi, J. P., Han, G., Wehn, P. M., Cao, Z., Du, X., Cheng, T., Czerwinski, R. M., Dixon, D. D., Goggin, B. S., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0473 · Cited by 336
Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy
Marengo, B., Nitti, M., Furfaro, A. L., Colla, R., Ciucis, C. D., Marinari, U. M., Pronzato, M. A., Traverso, N., & Domenicotti, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6235641 · Cited by 327
Single-Cell RNA Sequencing Maps Endothelial Metabolic Plasticity in Pathological Angiogenesis
Rohlenová, K., Goveia, J., García‐Caballero, M., Subramanian, A., Kalucka, J. M., Treps, L., Falkenberg, K. D., de Rooij, L. P. M. H., Zheng, Y., Lin, L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.009 · Cited by 317
Hypoxia-inducible factors and the regulation of lipid metabolism
Mylonis, I., Simos, G., & Paraskeva, E. (2019) · Cells · doi:10.3390/cells8030214 · Cited by 316
Allosteric inhibition of hypoxia inducible factor-2 with small molecules
Scheuermann, T. H., Li, Q., Ma, H.-W., Key, J., Zhang, L., Chen, R., Garcia, J. A., Naidoo, J., Longgood, J., Frantz, D. E., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1185 · Cited by 315
Falchook, G. S., Infante, J. R., Arkenau, H., Patel, M. R., Dean, E. J., Borazanci, E. H., Brenner, A. J., Cook, N., Lopez, J., Pant, S., et al. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.100797 · Cited by 313
Tap, W. D., Pápai, Z., Tine, B. A. V., Attia, S., Ganjoo, K. N., Jones, R. L., Schuetze, S. M., Reed, D. R., Chawla, S. P., Riedel, R. F., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30381-9 · Cited by 304
Zadra, G., Ribeiro, C. F., Chetta, P., Ho, Y., Cacciatore, S., Gao, X., Syamala, S., Bango, C., Photopoulos, C., Huang, Y., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808834116 · Cited by 304
Ventura, R., Mordec, K., Waszczuk, J., Wang, Z., Lai, J., Fridlib, M., Buckley, D., Kemble, G., & Heuer, T. S. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.06.020 · Cited by 301
Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H(+) symporters
Marchiq, I., & Pouysségur, J. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1307-x · Cited by 300
Wood, S. M., Gleadle, J., Pugh, C. W., Hankinson, O., & Ratcliffe, P. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15117 · Cited by 289
Yang, X., Lu, Y., Hang, J., Zhang, J., Zhang, T., Huo, Y., Liu, J., Lai, S., Luo, D., Wang, L., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0111 · Cited by 289
von Pawel, J., von Roemeling, R., Gatzemeier, U., Boyer, M. J., Elisson, L. O., CLARK, P. I., Talbot, D., Rey, A. A., Butler, T. W., Hirsh, V., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.6.1351 · Cited by 285
Hypoxia-inducible factor 3 biology: complexities and emerging themes
Duan, C. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00315.2015 · Cited by 269 · cited 1×
“Among the best-studied HIF-3 a isoforms is inhibitory PAS domain protein (IPAS), which suppresses hypoxia-induced transcription by sequestering HIF-1 a and blocking HIF-1 a / b heterodimer formation (44 – 46).”
Sheng, S. L., Liu, J., Dai, Y., Sun, X. G., Xiong, X. P., & Huang, G. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08748.x · Cited by 263
Cancer associated fibroblasts in cancer development and therapy
Jia, H., Chen, X., Zhang, L., & Chen, M. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01688-0 · Cited by 262
Alqahtani, A., Choucair, K., Ashraf, M., Hamouda, D., Alloghbi, A., Khan, T. A., Senzer, N. N., & Nemunaitis, J. J. (2019) · Future Science OA · doi:10.4155/fsoa-2018-0115 · Cited by 260
Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy
Ye, Y., Hu, Q., Chen, H., Liang, K., Yuan, Y., Xiang, Y., Ruan, H., Zhang, Z., Song, A., Zhang, H., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0045-8 · Cited by 258
The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia
Ding, X., Wang, L., Zhang, X., Xu, J., Li, P., Liang, H. L., Zhang, X., Xie, L., Zhou, Z., Yang, J., et al. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01102-5 · Cited by 257
Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) Hydroxylases: Unique or Ubiquitous?
Strowitzki, M. J., Cummins, E. P., & Taylor, C. T. (2019) · Cells · doi:10.3390/cells8050384 · Cited by 255
Patterson, A. V., Ferry, D. M., Edmunds, S. J., Gu, Y., Singleton, R. S., Patel, K., Pullen, S. M., Hicks, K. O., Syddall, S. P., Atwell, G. J., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0478 · Cited by 253
Rischin, D., Peters, L., Fisher, R., Macann, A., Denham, J., Poulsen, M., Jackson, M., Kenny, L., Penniment, M., Corry, J., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.072 · Cited by 253
Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs
Phillips, R. M. (2016) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-015-2920-7 · Cited by 248
A RNA antagonist of hypoxia-inducible factor-1α, EZN-2968, inhibits tumor cell growth
Greenberger, L. M., Horak, I. D., Filpula, D., Sapra, P., Westergaard, M., Frydenlund, H. F., Albæk, C., Schrøder, H., & Ørum, H. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0510 · Cited by 245
Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors
Dunbar, E. M., Coats, B. S., Shroads, A. L., Langaee, T., Lew, A., Forder, J. R., Shuster, J. J., Wagner, D. A., & Stacpoole, P. W. (2014) · Investigational New Drugs · doi:10.1007/s10637-013-0047-4 · Cited by 241
Seo, J., Jeong, D., Park, J., Lee, K., Fukuda, J., & Chun, Y. (2020) · Communications Biology · doi:10.1038/s42003-020-01367-5 · Cited by 237
Hayashi, M., Sakata, M., Takeda, T., Yamamoto, T., Okamoto, Y., Sawada, K., Kimura, A., Minekawa, R., Tahara, M., Tasaka, K., et al. (2004) · Journal of Endocrinology · doi:10.1677/joe.1.05599 · Cited by 234
Zhang, P., Yao, Q., Lu, L., Li, Y., Chen, P.-J., & Duan, C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.011 · Cited by 232
Tumor hypoxia: From basic knowledge to therapeutic implications
Liao, C., Liu, X., Zhang, C., & Zhang, Q. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.12.011 · Cited by 223
Saxena, K., & Jolly, M. K. (2019) · Biomolecules · doi:10.3390/biom9080339 · Cited by 223
Dichloroacetate induces apoptosis in endometrial cancer cells
Wong, J. Y. Y., Huggins, G. S., Debidda, M., Munshi, N. C., & Vivo, I. D. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.01.038 · Cited by 220
Loomba, R., Mohseni, R., Lucas, K. J., Gutierrez, J. A., Perry, R. G., Trotter, J. F., Rahimi, R. S., Harrison, S. A., Ajmera, V., Wayne, J. D., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.025 · Cited by 220
Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria
Thomas, L. W., & Ashcroft, M. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03039-y · Cited by 219
Roles of the human hypoxia-inducible factor (HIF)-3α variants in the hypoxia response
Heikkilä, M., Pasanen, A., Kivirikko, K. I., & Myllyharju, J. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0679-5 · Cited by 213
Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?
Belhabib, I., Zaghdoudi, S., Lac, C., Bousquet, C., & Jean, C. (2021) · Cancers · doi:10.3390/cancers13143466 · Cited by 210
Oxygen availability and metabolic reprogramming in cancer
Xie, H. J., & Simon, M. C. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.799973 · Cited by 207
Jenke, R., Reßing, N., Hansen, F. K., Aigner, A. M., & Büch, T. (2021) · Cancers · doi:10.3390/cancers13040634 · Cited by 198
Borad, M. J., Reddy, S. G., Bahary, N., Uronis, H. E., Sigal, D., Cohn, A. L., Schelman, W. R., Stephenson, J., Chiorean, E. G., Rosen, P. J., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.7504 · Cited by 197
Endothelial Dysfunction Driven by Hypoxia—The Influence of Oxygen Deficiency on NO Bioavailability
Janaszak‐Jasiecka, A., Siekierzycka, A., Płoska, A., Dobrucki, I. T., & Kalinowski, L. (2021) · Biomolecules · doi:10.3390/biom11070982 · Cited by 197
HIF1/2α mediates hypoxia-induced LDHA expression in human pancreatic cancer cells
Cui, X., Han, Z., He, S., Wu, X., Chen, T., Shao, C., Chen, D., Su, N., Chen, Y.-M., Wang, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15266 · Cited by 191
The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis
Bakleh, M. Z., & Zen, A. A. H. (2025) · Cells · doi:10.3390/cells14090673 · Cited by 190
Lactate stimulates endothelial cell migration
Beckert, S., Farrahi, F., Aslam, R. S., Scheuenstuhl, H., Königsrainer, A., Hussain, M., & Hunt, T. K. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1743-6109.2006.00127.x · Cited by 187
Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function
Caslin, H. L., Abebayehu, D., Pinette, J. A., & Ryan, J. J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.688485 · Cited by 187
FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors
Fallah, J., Brave, M. H., Weinstock, C., Mehta, G. U., Bradford, D., Gittleman, H., Bloomquist, E. W., Charlab, R., Hamed, S. S., Miller, C. P., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1054 · Cited by 180
AQ4N: a new approach to hypoxia-activated cancer chemotherapy
Patterson, L. H., & McKeown, S. R. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1564 · Cited by 180
Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells
Madhok, B., Yeluri, S., Perry, S., Hughes, T. A., & Jayne, D. G. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605701 · Cited by 180
Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death
Danielli, M., Perne, L., Jarc Jovičić, E., & Petan, T. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1104725 · Cited by 180
Li, Y., Yang, W., Zheng, Y., Dai, W., Ji, J., Wu, L., Cheng, Z., Zhang, J., Li, J., Xu, X., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02567-z · Cited by 179
Lang, S. A., Gaumann, A. K. A., Koehl, G. E., Seidel, U., Bataille, F., Klein, D., Ellis, L. M., Bolder, U., Hofstaedter, F., Schlitt, H. J., et al. (2007) · International Journal of Cancer · doi:10.1002/ijc.22442 · Cited by 170
da Motta, L. L., Ledaki, I., Purshouse, K. R., Haider, S. A., Bastiani, M. A. D., Baban, D., Morotti, M., Steers, G., Wigfield, S., Bridges, E., et al. (2016) · Oncogene · doi:10.1038/onc.2016.184 · Cited by 160
Alwarawrah, Y., Hughes, P. F., Loiselle, D. R., Carlson, D. A., Darr, D. B., Jordan, J. L., Xiong, J., Hunter, L., Dubois, L. G., Thompson, J. W., et al. (2016) · Cell chemical biology · doi:10.1016/j.chembiol.2016.04.011 · Cited by 159
Tannir, N. M., Agarwal, N., Porta, C., Lawrence, N. J., Motzer, R. J., McGregor, B. A., Lee, R. J., Jain, R., Davis, N. B., Appleman, L. J., et al. (2022) · JAMA Oncology · doi:10.1001/jamaoncol.2022.3511 · Cited by 158
Speer, R. E., Karuppagounder, S. S., Basso, M., Sleiman, S. F., Kumar, A., Brand, D., Smirnova, N., Gazaryan, I. G., Khim, S. J., & Ratan, R. R. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.026 · Cited by 157
Seguin, F., Carvalho, M. A., Bastos, D. C., Agostini, M., Zecchin, K. G., Flores, M. P. A., Chudzinski-Tavassi, A. M., Coletta, R. D., & Graner, E. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.355 · Cited by 154
Hypoxia induces hexokinase II gene expression in human lung cell line A549
Riddle, S. R., Ahmad, A. M., Ahmad, S., Deeb, S. S., Malkki, M., Schneider, B. K., Allen, C. B., & White, C. W. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.278.2.l407 · Cited by 153
The crosstalk between HIFs and mitochondrial dysfunctions in cancer development
Bao, X., Zhang, J., Huang, G., Yan, J., Xu, C., Dou, Z., Sun, C., & Zhang, H. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-03505-1 · Cited by 152
Bailey, C. M., Liu, Y., Liu, M., Du, X., Devenport, M., Zheng, P., Liu, Y., & Wang, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci150846 · Cited by 151
Hu, K., Babapoor-Farrokhran, S., Rodrigues, M. W., Deshpande, M. M., Puchner, B., Kashiwabuchi, F., Hassan, S. J., Asnaghi, L., Handa, J. T., Merbs, S. L., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.6868 · Cited by 150
Magar, A. G., Morya, V. K., Kwak, M. K., Oh, J. U., & Noh, K.-C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063313 · Cited by 150
Zhang, J., Yao, M., Xia, S., Zeng, F., & Liu, Q. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00682-7 · Cited by 150
Role of hypoxia in the tumor microenvironment and targeted therapy
Chen, G., Wu, K., Li, H., Xia, D., & He, T. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.961637 · Cited by 148
Kelly, W., Duque, A. E. D., Michalek, J. E., Konkel, B., Caflisch, L., Chen, Y., Pathuri, S. C., Madhusudanannair-Kunnuparampil, V., Floyd, J., & Brenner, A. J. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-2807 · Cited by 147
Vascular normalisation as the stepping stone into tumour microenvironment transformation
Magnussen, A. L., & Mills, I. G. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01330-z · Cited by 146
Bigos, K. J. A., Quiles, C. G., Lunj, S., Smith, D. J., Krause, M., Troost, E. G. C., West, C., Hoskin, P., & Choudhury, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1331355 · Cited by 146
Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
Schcolnik‐Cabrera, A., Chávez-Blanco, A. D., Domínguez-Gómez, G., Taja‐Chayeb, L., Morales‐Bárcenas, R., Trejo‐Becerril, C., Pérez‐Cárdenas, E., González‐Fierro, A., & Dueñas‐González, A. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1471132 · Cited by 143
Wang, B., Pei, J., Xu, S., Liu, J., & Yu, J. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-02994-0 · Cited by 140
Metabolic Reprogramming of Cancer Associated Fibroblasts: The Slavery of Stromal Fibroblasts
Avagliano, A., Granato, G., Ruocco, M. R., Romano, V., Belviso, I., Carfora, A., Montagnani, S., & Arcucci, A. (2018) · BioMed Research International · doi:10.1155/2018/6075403 · Cited by 139
Augustin, R. C., Delgoffe, G. M., & Najjar, Y. G. (2020) · Cancers · doi:10.3390/cancers12123802 · Cited by 139
Ma, Z., Xiang, X., Li, S., Xie, P., Gong, Q., Goh, B.-C., & Wang, L. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.09.011 · Cited by 138
Qannita, R. A., Alalami, A., Harb, A. A., Aleidi, S. M., Taneera, J., Abu‐Gharbieh, E., El‐Huneidi, W., Saleh, M. A., Alzoubi, K. H., Semreen, M. H., et al. (2024) · Pharmaceuticals · doi:10.3390/ph17020195 · Cited by 137
Albanese, A., Daly, L. A., Mennerich, D., Kietzmann, T., & Sée, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010268 · Cited by 136
Sanjuán-Pla, A., Cervera, A. M., Apostolova, N., Garcia-Bou, R., Víctor, V. M., Murphy, M. P., & McCreath, K. J. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.088 · Cited by 134
Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance
Belisario, D. C., Kopecka, J., Pasino, M., Akman, M., De Smaele, E., Donadelli, M., & Riganti, C. (2020) · Cells · doi:10.3390/cells9122598 · Cited by 133
Zhang, J., Cao, J., Ma, S., Dong, R., Meng, W., Ying, M., Weng, Q., Chen, Z., Ma, J., Fang, Q., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1856 · Cited by 133
CAFs orchestrates tumor immune microenvironment—A new target in cancer therapy?
Zhang, C., Fei, Y., Wang, H., Hu, S., Liu, C., Hu, R., & Du, Q. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1113378 · Cited by 132
Agostini, M., Almeida, L. Y., Bastos, D. C., Ortega, R. M., Moreira, F. S., Seguin, F., Zecchin, K. G., Raposo, H. F., Oliveira, H. C. F., Amoêdo, N. D., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1136 · Cited by 131
Albertella, M. R., Loadman, P. M., Jones, P. H., Phillips, R. M., Rampling, R., Burnet, N. G., Alcock, C., Anthoney, A., Vjaters, E., Dunk, C. R., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4020 · Cited by 131
‘Reverse Warburg effect’ of cancer‑associated fibroblasts (Review)
Liang, L., Li, W., Li, X., Jin, X., Liao, Q., Li, Y., & Zhou, Y. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5357 · Cited by 131
Kai, A. K., Chan, L., Lo, R. C., Lee, J. M., Wong, C. C., Wong, J. C., & Ng, I. O. (2016) · Hepatology · doi:10.1002/hep.28577 · Cited by 128
DiSilvestro, P. A., Ali, S., Craighead, P. S., Lucci, J. A., Lee, Y.-C., Cohn, D. E., Spirtos, N. M., Tewari, K. S., Muller, C., Gajewski, W. H., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.4265 · Cited by 127
Pasanen, A., Heikkilä, M. M., Rautavuoma, K., Hirsilä, M., Kivirikko, K. I., & Myllyharju, J. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.04.008 · Cited by 125
Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation
Li, T., Mao, C., Wang, X., Shi, Y., & Tao, Y. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01733-5 · Cited by 125
Decoding tumor angiogenesis: pathways, mechanisms, and future directions in anti-cancer strategies
Liu, X., Zhang, J., Yi, T., Li, H., Tang, X., Liu, D., Wu, D., & Li, Y. (2025) · Biomarker Research · doi:10.1186/s40364-025-00779-x · Cited by 125
Benito, J., Shi, Y., Szymanska, B., Carol, H., Boehm, I., Lu, H., Konoplev, S. N., Fang, W., Zweidler‐McKay, P. A., Campana, D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023108 · Cited by 122
Makino, Y., Uenishi, R., Okamoto, K., Isoe, T., Hosono, O., Tanaka, H., Kanopka, A., Poellinger, L., Haneda, M., & Morimoto, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700732200 · Cited by 120 · cited 1×
“In early or transient hypoxia, HIF-3 a may act as a negative feedback regulator, dampening excessive HIF-1 a and HIF-2 a signaling (49, 50).”
Role of Glutamine in Cancer: Therapeutic and Imaging Implications: FIGURE 1.
Rajagopalan, K. N., & DeBerardinis, R. J. (2011) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.084244 · Cited by 120
Konopleva, M., Thall, P. F., Yi, C. A., Borthakur, G. M., Coveler, A. L., Bueso‐Ramos, C. E., Benito, J., Konoplev, S. N., Gu, Y., Ravandi, F., et al. (2015) · Haematologica · doi:10.3324/haematol.2014.118455 · Cited by 120
Therapeutic efficacy of FASN inhibition in preclinical models of HCC
Wang, H., Zhou, Y., Xu, H., Wang, X., Zhang, Y., Shang, R., O’Farrell, M., Roessler, S. K., Sticht, C., Stahl, A., et al. (2022) · Hepatology · doi:10.1002/hep.32359 · Cited by 120
Reengineering the Tumor Vasculature: Improving Drug Delivery and Efficacy
Stylianopoulos, T., Munn, L. L., & Jain, R. K. (2018) · Trends in Cancer · doi:10.1016/j.trecan.2018.02.010 · Cited by 119
Hypoxia signaling in cancer: Implications for therapeutic interventions
Zhuang, Y., Liu, K., He, Q., Gu, X., Jiang, C., & Wu, J. (2023) · MedComm · doi:10.1002/mco2.203 · Cited by 119
Mandl, M., & Depping, R. (2014) · Molecular Medicine · doi:10.2119/molmed.2014.00032 · Cited by 119
Mazumder, S., Higgins, P. J., & Samarakoon, R. (2023) · Cancers · doi:10.3390/cancers15041316 · Cited by 118
Haugrud, A. B., Zhuang, Y., Coppock, J. D., & Miskimins, W. K. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3128-y · Cited by 115
Lee, C., Motzer, R. J., Emamekhoo, H., Matrana, M. R., Percent, I. J., Hsieh, J. J.-D., Hussain, A., Vaishampayan, U. N., Liu, S. T., McCune, S. L., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-0061 · Cited by 115
Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy
Shurin, M. R., & Umansky, V. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159473 · Cited by 113
Leblond, M. M., Gérault, A. N., Corroyer‐Dulmont, A., MacKenzie, E. T., Petit, E., Bernaudin, M., & Valable, S. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1056442 · Cited by 113
FABP7 is a key metabolic regulator in HER2+ breast cancer brain metastasis
Cordero, Á., Kanojia, D., Miska, J. M., Panek, W. K., Xiao, A., Han, Y., Bonamici, N. J., Zhou, W., Xiao, T., Wu, M., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0893-4 · Cited by 113
Salman, S., Meyers, D. J., Wicks, E. E., Lee, S. N., Datan, E., Thomas, A. M., Anders, N. M., Hwang, Y., Lyu, Y., Yang, Y., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156774 · Cited by 111 · cited 1×
“This combination therapy also promoted durable immune memory, preventing tumor recurrence (226).”
Mack, P. C., Redman, M. W., Chansky, K., Williamson, S. K., Farneth, N. C., Lara, P. N., Franklin, W. A., Le, Q., Crowley, J. J., & Gandara, D. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.0662 · Cited by 110
Hutt, D. M., Roth, D. M., Vignaud, H., Cullin, C., & Bouchecareilh, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106224 · Cited by 109 · cited 3×
“HDACi reduce HIF output by blocking HIF transactivation and/or lowering HIF-1 a protein (often via translational control) (201 – 203), while BET inhibitors (e.g., JQ1, OTX015/MK-8628, molibresib, pelabresib) limit recruitment of BRD proteins to hypoxia-responsive promoters, diminishing expression…”
InfluentialFath, D. M., Kong, X., Liang, D., Lin, Z., Chou, A. D., Jiang, Y., Fang, J., Caro, J., & Sang, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600456200 · Cited by 108
Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment
Kim, I., Choi, S., Yoo, S., Lee, M., & Kim, I. (2022) · Cancers · doi:10.3390/cancers14143321 · Cited by 107
Tirapazamine: a bioreductive anticancer drug that exploits tumour hypoxia
Denny, W. A., & Wilson, W. R. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.12.2889 · Cited by 104
Hao, X., Ren, Y., Feng, M., Wang, Q., & Wang, Y. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111798 · Cited by 101
Gillespie, D. L., Whang, K., Ragel, B. T., Flynn, J. R., Kelly, D. A., & Jensen, R. L. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2692 · Cited by 101
The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit?
Abla, H., Sollazzo, M., Gasparre, G., Iommarini, L., & Porcelli, A. M. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.031 · Cited by 99
Harding, J. J., Telli, M. L., Münster, P. N., Voss, M. H., Infante, J. R., DeMichele, A. M., Dunphy, M. P., Le, M. H., Molineaux, C., Orford, K. W., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1204 · Cited by 98
Lee, K. Y., Gesta, S., Boucher, J., Wang, X. L., & Kahn, C. R. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.006 · Cited by 97
Luo, F., Lu, F.-T., Cao, J.-X., Ma, W.-J., Xia, Z.-F., Zhan, J.-H., Zeng, K.-M., Huang, Y., Zhao, H.-Y., & Zhang, L. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.01.027 · Cited by 95
Zhu, Y., Li, T., da Silva, S. R., Lee, J. J., Lu, C., Eoh, H., Jung, J. U., & Gao, S. (2017) · mBio · doi:10.1128/mbio.01179-17 · Cited by 92
Avolio, R., Matassa, D. S., Criscuolo, D., Landriscina, M., & Esposito, F. (2020) · Biomolecules · doi:10.3390/biom10010135 · Cited by 90
Fontaine, F. R., Overman, J. P., & François, M. (2015) · Cell Regeneration · doi:10.1186/s13619-015-0015-x · Cited by 89
Kao, T.-W., Bai, G.-H., Wang, T.-L., Shih, I.-M., Chuang, C.-M., Lo, C.-L., Tsai, M.-C., Chiu, L.-Y., Lin, C.-C., & Shen, Y.-A. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02724-y · Cited by 89
Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection
Huang, X., Zhao, L., & Peng, R. (2022) · Biomolecules · doi:10.3390/biom13010050 · Cited by 88
Gouda, M. A., Voss, M. H., Tawbi, H. A., Gordon, M. S., Tykodi, S. S., Lam, E. T., Vaishampayan, U. N., Tannir, N. M., Chaves, J. M., Nikolinakos, P. G., et al. (2025) · ESMO Open · doi:10.1016/j.esmoop.2025.104536 · Cited by 88
Effects of Histone Deacetylase Inhibitors on HIF-1
Liang, D., Kong, X., & Sang, N. (2006) · Cell Cycle · doi:10.4161/cc.5.21.3409 · Cited by 85
Singleton, R. S., Guise, C. P., Ferry, D. M., Pullen, S. M., Dorie, M. J., Brown, J. M., Patterson, A. V., & Wilson, W. R. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4023 · Cited by 85
Acidic extracellular pH promotes epithelial mesenchymal transition in Lewis lung carcinoma model
Suzuki, A., Maeda, T., Baba, Y., Shimamura, K., & Kato, Y. (2014) · Cancer Cell International · doi:10.1186/s12935-014-0129-1 · Cited by 83
Chintala, S., Najrana, T., Tóth, K., Cao, S., Durrani, F. A., Пили, Р., & Rustum, Y. M. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-293 · Cited by 81
Flagged first, then by citations
Research works printed but not linked: 8
- Calorini, 2012, Extracellular acidity as favouring factor of tumor progression and metastatic dissemination, Exp Oncol, 34, 79
- Gao, 2015, Acidic extracellular microenvironment promotes the invasion and cathepsin B secretion of PC-3 cells, Int J Clin Exp Med, 8
- Jarc, 2019, Lipid droplets and the management of cellular stress, Yale J Biol Med, 92
- Leek, 2002, Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer, Cancer Res, 62
- Boucher, 1990, Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy, Cancer Res, 50
- Zhang, 2025, Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer, Cell Mol Biol Lett, 30, 10.1186/s11658-024-00682-7 · DOI
- Han, 2023, Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases, Front Pharmacol, 14, 10.3389/fphar.2023.1275000 · DOI
- Hay, 2003, Structure-activity relationships of 1, 2, 4-benzotriazine 1, 4-dioxides as hypoxia-selective analogues of tirapazamine, J Med Chem, 46, 10.1021/jm020367 · DOI
Cited by
Sorted by citations
Henrykowska, G., Bartusik-Aebisher, D., Dynarowicz, K., Ramesh, T. S., Smolak, B., & Aebisher, D. (2026) · Pharmaceuticals · doi:10.3390/ph19071041 · Cited by 1
“As tumors grow beyond the reach of blood vessels, hypoxia leads to the stabilization of hypoxia-inducible factor 1 α (HIF-1 α ), which then induces the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis [54].”
Glycolytic reprogramming and the EMT drive cervical cancer progression via the NQO1/HIF1α-SIX1 axis
Zhu, G., Piao, Z., Gao, Y., Cong, X., Wei, P., Han, A., Zhou, H., Lin, Z., & Jin, T. (2026) · iScience · doi:10.1016/j.isci.2026.117007 · Cited by 1
Hammouz, R. Y., Maciejek, K., & Bednarek, A. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156740
Chronobiology of Cancer: How Aging Fuels Oncogenesis at the Molecular Level
Singh, A., Misra, A., & Zaheer, S. (2026) · Aging and Cancer · doi:10.1002/aac2.70027
Self-citationLi, X., Yang, K., Liang, X., Qi, F., & Lv, Y. (2026) · Precision medicine and engineering. · doi:10.1016/j.preme.2026.100085
Metadata
- Authors
- Sureka, N., Maheshwari, R., Agravat, A., Singhal, S., Zaman, S., Rishi, B., Siraj, F., Zaheer, S., & Misra, A.
- Affiliations
- Safdarjang Hospital (IN)
- Department of Pathology, Pandit Deendayal Upadhyay (PDU) Medical College
- Indian Council of Medical Research (IN)
- National Institute of Child Health (PK)
- Corresponding author
- Zaheer, Sufian
- Misra, Aroonima
- ORCID
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2026-03-31
- Volume
- 16
- Pages
- 1771365-1771365
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC13076347
- OpenAlex
- W7143706570
- Cited by
- 11
- References
- 313
- Citations by year
- 2026: 11
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- tumor hypoxia, hypoxic tumor microenvironment, metabolic reprogramming, hypoxia-inducible factor, HIF-1α, HIF-2α, aerobic glycolysis, glutamine metabolism, lipid metabolism, redox homeostasis, reactive oxygen species, epithelial-mesenchymal transition, extracellular matrix remodeling, metastasis, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, tumor immunosuppression, immune evasion, treatment resistance, HIF-targeted therapy, precision oncology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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