Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer

Nature Reviews Cardiology volume 19, pages 414–425 (2022)Cite this article

Subjects

Abstract

Cardiovascular disease and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology has revealed that these seemingly disparate disease processes are intertwined, owing to the cardiovascular sequelae of anticancer therapies, shared risk factors that predispose individuals to both cardiovascular disease and cancer, as well the possible potentiation of cancer growth by cardiac dysfunction. As a result, interest has increased in understanding the fundamental biological mechanisms that are central to the relationship between cardiovascular disease and cancer. Metabolism, appropriate regulation of energy, energy substrate utilization, and macromolecular synthesis and breakdown are fundamental processes for cellular and organismal survival. In this Review, we explore the emerging data identifying metabolic dysregulation as an important theme in cardio-oncology. We discuss the growing recognition of metabolic reprogramming in cardiovascular disease and cancer and view the novel area of cardio-oncology through the lens of metabolism.

Key points

  • Metabolic remodelling is a defining feature of both cardiovascular diseases and tumours.

  • Metabolic dysregulation of cancer cells extends beyond the tumour microenvironment and can lead to both systemic and cardiac-specific consequences.

  • Cardiovascular disease and cancer share several risk factors, including diabetes mellitus, dyslipidaemia, cachexia and an impaired immune response.

  • Anticancer therapies can result in adverse cardiac events, including acute myocardial infarction and heart failure.

  • Targeting metabolic features of cancer cells might limit tumour growth and also protect the heart against adverse remodelling.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The central role of metabolic remodelling in cardiovascular disease and cancer.
Fig. 2: Metabolism bridges cancer and cardiovascular disease.
Fig. 3: Putative mechanisms of cardio-onco-metabolic remodelling.
Fig. 4: Accumulation of somatic mutations changes the metabolic profile of tumours and influences the cardiovascular system.
Fig. 5: Metabolic targets and interventions in cardiovascular disease and cancer.

Similar content being viewed by others

References

  1. Moslehi, J. J. Cardiovascular toxic effects of targeted cancer therapies. N. Engl. J. Med. 375, 1457–1467 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. de Boer, R. A. et al. Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur. J. Heart Fail. 22, 2272–2289 (2020).

    Article  PubMed  Google Scholar 

  3. Aboumsallem, J. P., Moslehi, J. & de Boer, R. A. Reverse cardio-oncology: cancer development in patients with cardiovascular disease. J. Am. Heart Assoc. 9, e013754 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Karlstaedt, A. et al. Oncometabolite D-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc. Natl Acad. Sci. USA 113, 10436–10441 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Akbay, E. A. et al. D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev. 28, 479–490 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Meijers, W. C. & de Boer, R. A. Common risk factors for heart failure and cancer. Cardiovasc. Res. 115, 844–853 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lau, E. S. et al. Cardiovascular risk factors are associated with future cancer. JACC CardioOncol 3, 48–58 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mariotto, A. B. et al. Long-term survivors of childhood cancers in the United States. Cancer Epidemiol. Biomark. Prev. 18, 1033–1040 (2009).

    Article  Google Scholar 

  10. Miller, K. D. et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J. Clin. 66, 271–289 (2016).

    Article  PubMed  Google Scholar 

  11. Mulrooney, D. A. et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339, b4606 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nathan, P. C. et al. Medical care in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J. Clin. Oncol. 26, 4401–4409 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ward, E., DeSantis, C., Robbins, A., Kohler, B. & Jemal, A. Childhood and adolescent cancer statistics, 2014. CA Cancer J. Clin. 64, 83–103 (2014).

    Article  PubMed  Google Scholar 

  14. Avraham, S. et al. Early cardiac remodeling promotes tumor growth and metastasis. Circulation 142, 670–683 (2020).

    Article  CAS  PubMed  Google Scholar 

  15. Meijers, W. C. et al. Heart failure stimulates tumor growth by circulating factors. Circulation 138, 678–691 (2018).

    Article  CAS  PubMed  Google Scholar 

  16. Matetic, A. et al. Impact of cancer diagnosis on causes and outcomes of 5.9 million US patients with cardiovascular admissions. Int. J. Cardiol. 341, 76–83 (2021).

    Article  PubMed  Google Scholar 

  17. Karlstaedt, A., Barrett, M., Hu, R., Gammons, S. T. & Ky, B. Cardio-oncology: understanding the intersections between cardiac metabolism and cancer biology. JACC Basic. Transl. Sci. 6, 705–718 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Young, M. E. et al. Proposed regulation of gene expression by glucose in rodent heart. Gene Regul. Syst. Bio. 1, 251–262 (2007).

    PubMed  PubMed Central  Google Scholar 

  19. Young, M. E., Laws, F. A., Goodwin, G. W. & Taegtmeyer, H. Reactivation of peroxisome proliferator-activated receptor α is associated with contractile dysfunction in hypertrophied rat heart. J. Biol. Chem. 276, 44390–44395 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Taegtmeyer, H. et al. Assessing cardiac metabolism: a scientific statement from the American Heart Association. Circ. Res. 118, 1659–1701 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Leu, M. et al. Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome. Sci. Rep. 11, 4578 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yurista, S. R., Nguyen, C. T., Rosenzweig, A., de Boer, R. A. & Westenbrink, B. D. Ketone bodies for the failing heart: fuels that can fix the engine? Trends Endocrinol. Metab. 32, 814–826 (2021).

    Article  CAS  PubMed  Google Scholar 

  23. Yurista, S. R. et al. Therapeutic potential of ketone bodies for patients with cardiovascular disease: JACC state-of-the-art review. J. Am. Coll. Cardiol. 77, 1660–1669 (2021).

    Article  CAS  PubMed  Google Scholar 

  24. Benjamin, J. S. et al. A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome. Proc. Natl Acad. Sci. USA 114, 125–130 (2017).

    Article  CAS  PubMed  Google Scholar 

  25. Newman, J. C. & Verdin, E. Ketone bodies as signaling metabolites. Trends Endocrinol. Metab. 25, 42–52 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Cannon, M. V. et al. Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization. EMBO Mol. Med. 7, 1229–1243 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ngoh, G. A., Facundo, H. T., Zafir, A. & Jones, S. P. O-GlcNAc signaling in the cardiovascular system. Circ. Res. 107, 171–185 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Murashige, D. et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370, 364–368 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Selvaraj, S., Kelly, D. P. & Margulies, K. B. Implications of altered ketone metabolism and therapeutic ketosis in heart failure. Circulation 141, 1800–1812 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lauzier, B. et al. Metabolic effects of glutamine on the heart: anaplerosis versus the hexosamine biosynthetic pathway. J. Mol. Cell Cardiol. 55, 92–100 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Sun, H. et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation 133, 2038–2049 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tonjes, M. et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat. Med. 19, 901–908 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371.e9 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim, J. & DeBerardinis, R. J. Mechanisms and implications of metabolic heterogeneity in cancer. Cell Metab. 30, 434–446 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

    Article  CAS  Google Scholar 

  36. Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519–530 (1927).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Koppenol, W. H., Bounds, P. L. & Dang, C. V. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat. Rev. Cancer 11, 325–337 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Hensley, C. T. et al. Metabolic heterogeneity in human lung tumors. Cell 164, 681–694 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gaude, E. & Frezza, C. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat. Commun. 7, 13041 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Katzir, R. et al. The landscape of tiered regulation of breast cancer cell metabolism. Sci. Rep. 9, 17760 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Lau, A. N. et al. Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma. eLife 9, e56782 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Najumudeen, A. K. et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat. Genet. 53, 16–26 (2021).

    Article  CAS  PubMed  Google Scholar 

  43. Osthus, R. C. et al. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J. Biol. Chem. 275, 21797–21800 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Duran, A. et al. The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis. Cancer Cell 13, 343–354 (2008).

    Article  CAS  PubMed  Google Scholar 

  45. Gurel, B. et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod. Pathol. 21, 1156–1167 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mossafa, H. et al. Non-Hodgkin’s lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis. Leuk. Lymphoma 47, 1885–1893 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Cantley, L. C. & Neel, B. G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl Acad. Sci. USA 96, 4240–4245 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jones, R. G. et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18, 283–293 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Lee, S. M., Kim, J. H., Cho, E. J. & Youn, H. D. A nucleocytoplasmic malate dehydrogenase regulates p53 transcriptional activity in response to metabolic stress. Cell Death Differ. 16, 738–748 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Palaskas, N. et al. 18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers. Cancer Res. 71, 5164–5174 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yue, M., Jiang, J., Gao, P., Liu, H. & Qing, G. Oncogenic MYC activates a feedforward regulatory loop promoting essential amino acid metabolism and tumorigenesis. Cell Rep. 21, 3819–3832 (2017).

    Article  CAS  PubMed  Google Scholar 

  52. Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Suzuki, T. et al. Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells. Cancer Gene Ther. https://doi.org/10.1038/s41417-021-00326-4 (2021).

    Article  PubMed  Google Scholar 

  54. Doherty, J. R. et al. Blocking lactate export by inhibiting the Myc target MCT1 disables glycolysis and glutathione synthesis. Cancer Res. 74, 908–920 (2014).

    Article  CAS  PubMed  Google Scholar 

  55. Koelwyn, G. J. et al. Myocardial infarction accelerates breast cancer via innate immune reprogramming. Nat. Med. 26, 1452–1458 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Donath, M. Y. & Shoelson, S. E. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 11, 98–107 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Stentz, F. B., Umpierrez, G. E., Cuervo, R. & Kitabchi, A. E. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 53, 2079–2086 (2004).

    Article  CAS  PubMed  Google Scholar 

  58. Esposito, K. et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289, 1799–1804 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Bellinger, A. M. et al. Cardio-oncology: how new targeted cancer therapies and precision medicine can inform cardiovascular discovery. Circulation 132, 2248–2258 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Asnani, A. et al. Preclinical models of cancer therapy-associated cardiovascular toxicity: a scientific statement from the American Heart Association. Circ. Res. 129, e21–e34 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Moslehi, J., Zhang, Q. & Moore, K. J. Crosstalk between the heart and cancer: beyond drug toxicity. Circulation 142, 684–687 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Koelwyn, G. J., Aboumsallem, J. P., Moore, K. J. & de Boer, R. A. Reverse cardio-oncology: exploring the effects of cardiovascular disease on cancer pathogenesis. J. Mol. Cell Cardiol. 163, 1–8 (2021).

    Article  PubMed  CAS  Google Scholar 

  63. Tocchetti, C. G. et al. Cardiac dysfunction in cancer patients: beyond direct cardiomyocyte damage of anticancer drugs: novel cardio-oncology insights from the joint 2019 meeting of the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart. Cardiovasc. Res. 116, 1820–1834 (2020).

    Article  CAS  PubMed  Google Scholar 

  64. Tini, G. et al. Cancer mortality in trials of heart failure with reduced ejection fraction: a systematic review and meta-analysis. J. Am. Heart Assoc. 9, e016309 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. de Boer, R. A. et al. A new classification of cardio-oncology syndromes. Cardiooncology 7, 24 (2021).

    PubMed  PubMed Central  Google Scholar 

  66. de Wit, S. & de Boer, R. A. From studying heart disease and cancer simultaneously to reverse cardio-oncology. Circulation 144, 93–95 (2021).

    Article  PubMed  Google Scholar 

  67. Koene, R. J., Prizment, A. E., Blaes, A. & Konety, S. H. Shared risk factors in cardiovascular disease and cancer. Circulation 133, 1104–1114 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  68. de Boer, R. A., Meijers, W. C., van der Meer, P. & van Veldhuisen, D. J. Cancer and heart disease: associations and relations. Eur. J. Heart Fail. 21, 1515–1525 (2019).

    Article  PubMed  Google Scholar 

  69. Pfeffer, T. J., Pietzsch, S. & Hilfiker-Kleiner, D. Common genetic predisposition for heart failure and cancer. Herz 45, 632–636 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Masoudkabir, F. et al. Cardiovascular disease and cancer: evidence for shared disease pathways and pharmacologic prevention. Atherosclerosis 263, 343–351 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gibson, C. J. et al. Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma. J. Clin. Oncol. 35, 1598–1605 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Libby, P. et al. Clonal hematopoiesis: crossroads of aging, cardiovascular disease, and cancer: JACC review topic of the week. J. Am. Coll. Cardiol. 74, 567–577 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Calvillo-Arguelles, O. et al. Connections between clonal hematopoiesis, cardiovascular disease, and cancer: a review. JAMA Cardiol. 4, 380–387 (2019).

    Article  PubMed  Google Scholar 

  74. Jaiswal, S. & Ebert, B. L. Clonal hematopoiesis in human aging and disease. Science 366, eaan4673 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Haring, B. et al. Healthy lifestyle and clonal hematopoiesis of indeterminate potential: results from the Women’s Health Initiative. J. Am. Heart Assoc. 10, e018789 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Dorsheimer, L. et al. Association of mutations contributing to clonal hematopoiesis with prognosis in chronic ischemic heart failure. JAMA Cardiol. 4, 25–33 (2019).

    Article  PubMed  Google Scholar 

  78. Buscarlet, M. et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 130, 753–762 (2017).

    Article  CAS  PubMed  Google Scholar 

  79. Honigberg, M. C. et al. Premature menopause, clonal hematopoiesis, and coronary artery disease in postmenopausal women. Circulation 143, 410–423 (2021).

    Article  PubMed  Google Scholar 

  80. Fuster, J. J. et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355, 842–847 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wang, J. G. et al. Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner. Blood 118, 2366–2374 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bick, A. G. et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 586, 763–768 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hou, H. A. et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 119, 559–568 (2012).

    Article  CAS  PubMed  Google Scholar 

  84. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  CAS  PubMed  Google Scholar 

  85. Ridker, P. M. et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390, 1833–1842 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Buckley, L. F. & Abbate, A. Interleukin-1 blockade in cardiovascular diseases: a clinical update. Eur. Heart J. 39, 2063–2069 (2018).

    Article  CAS  PubMed  Google Scholar 

  87. Gottschlich, A., Endres, S. & Kobold, S. Therapeutic strategies for targeting IL-1 in cancer. Cancers (Basel) 13, 477 (2021).

    Article  CAS  Google Scholar 

  88. Nidorf, S. M. et al. Colchicine in patients with chronic coronary disease. N. Engl. J. Med. 383, 1838–1847 (2020).

    Article  CAS  PubMed  Google Scholar 

  89. Silvis, M. J. M. et al. Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels in chronic coronary disease: a LoDoCo2 biomarker substudy. Atherosclerosis 334, 93–100 (2021).

    Article  CAS  PubMed  Google Scholar 

  90. Yan, H. et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765–773 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Mardis, E. R. et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361, 1058–1066 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Dang, L. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739–744 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Koivunen, P. et al. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 483, 484–488 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Losman, J. A. et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 339, 1621–1625 (2013).

    Article  CAS  PubMed  Google Scholar 

  95. Fu, X. et al. 2-Hydroxyglutarate Inhibits ATP synthase and mTOR signaling. Cell Metab. 22, 508–515 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kohanbash, G. et al. Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J. Clin. Invest. 127, 1425–1437 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Bunse, L. et al. Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat. Med. 24, 1192–1203 (2018).

    Article  CAS  PubMed  Google Scholar 

  98. Kattih, B. et al. IDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction–a retrospective propensity score analysis. Leukemia 35, 1301–1316 (2021).

    Article  CAS  PubMed  Google Scholar 

  99. Rzem, R. et al. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc. Natl Acad. Sci. USA 101, 16849–16854 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kranendijk, M., Struys, E. A., Salomons, G. S., Van der Knaap, M. S. & Jakobs, C. Progress in understanding 2-hydroxyglutaric acidurias. J. Inherit. Metab. Dis. 35, 571–587 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kranendijk, M. et al. Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. Hum. Mutat. 31, 279–283 (2010).

    Article  PubMed  CAS  Google Scholar 

  102. Kranendijk, M. et al. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science 330, 336 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Maher, E. R. & Kaelin, W. G. Jr. von Hippel-Lindau disease. Medicine 76, 381–391 (1997).

    Article  CAS  PubMed  Google Scholar 

  104. Menendez-Montes, I. et al. Myocardial VHL-HIF signaling controls an embryonic metabolic switch essential for cardiac maturation. Dev. Cell 39, 724–739 (2016).

    Article  CAS  PubMed  Google Scholar 

  105. Smith, T. G. et al. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 3, e290 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Smith, T. G. et al. Mutation of the von Hippel-Lindau gene alters human cardiopulmonary physiology. Adv. Exp. Med. Biol. 605, 51–56 (2008).

    Article  CAS  PubMed  Google Scholar 

  107. Formenti, F. et al. Regulation of human metabolism by hypoxia-inducible factor. Proc. Natl Acad. Sci. USA 107, 12722–12727 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Slingo, M. et al. The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high-energy phosphate metabolism. Am. J. Physiol. Heart Circ. Physiol. 311, H759–H767 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Perrotta, S. et al. Effects of germline VHL deficiency on growth, metabolism, and mitochondria. N. Engl. J. Med. 382, 835–844 (2020).

    Article  CAS  PubMed  Google Scholar 

  110. Lei, L. et al. Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von Hippel-Lindau protein. Mol. Cell Biol. 28, 3790–3803 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Liu, S. J. et al. Genotype and phenotype correlation in von Hippel-Lindau disease based on alteration of the HIF-α binding site in VHL protein. Genet. Med. 20, 1266–1273 (2018).

    Article  CAS  PubMed  Google Scholar 

  112. Cho, H. et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature 539, 107–111 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Choueiri, T. K. & Kaelin, W. G. Jr. Targeting the HIF2-VEGF axis in renal cell carcinoma. Nat. Med. 26, 1519–1530 (2020).

    Article  CAS  PubMed  Google Scholar 

  114. Jonasch, E. et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N. Engl. J. Med. 385, 2036–2046 (2021).

    Article  CAS  PubMed  Google Scholar 

  115. Chen, W. et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature 539, 112–117 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ghosh, M. C. et al. Therapeutic inhibition of HIF-2α reverses polycythemia and pulmonary hypertension in murine models of human diseases. Blood 137, 2509–2519 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Baysal, B. E. et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287, 848–851 (2000).

    Article  CAS  PubMed  Google Scholar 

  118. Goncalves, J. et al. Loss of SDHB promotes dysregulated iron homeostasis, oxidative stress, and sensitivity to ascorbate. Cancer Res. 81, 3480–3494 (2021).

    Article  CAS  PubMed  Google Scholar 

  119. Astuti, D. et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am. J. Hum. Genet. 69, 49–54 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Burnichon, N. et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum. Mol. Genet. 19, 3011–3020 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Tomlinson, I. P. et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 30, 406–410 (2002).

    Article  CAS  PubMed  Google Scholar 

  122. Hol, J. A. et al. Renal cell carcinoma in young FH mutation carriers: case series and review of the literature. Fam. Cancer 19, 55–63 (2020).

    Article  CAS  PubMed  Google Scholar 

  123. Letouze, E. et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 23, 739–752 (2013).

    Article  CAS  PubMed  Google Scholar 

  124. Davili, Z., Johar, S., Hughes, C., Kveselis, D. & Hoo, J. Succinate dehydrogenase deficiency associated with dilated cardiomyopathy and ventricular noncompaction. Eur. J. Pediatr. 166, 867–870 (2007).

    Article  PubMed  Google Scholar 

  125. Bourgeron, T. et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat. Genet. 11, 144–149 (1995).

    Article  CAS  PubMed  Google Scholar 

  126. Reichmann, H. & Angelini, C. Single muscle fibre analyses in 2 brothers with succinate dehydrogenase deficiency. Eur. Neurol. 34, 95–98 (1994).

    Article  CAS  PubMed  Google Scholar 

  127. Rustin, P. et al. The investigation of respiratory chain disorders in heart using endomyocardial biopsies. J. Inherit. Metab. Dis. 16, 541–544 (1993).

    Article  CAS  PubMed  Google Scholar 

  128. Ferreira, C. R., van Karnebeek, C. D. M., Vockley, J. & Blau, N. A proposed nosology of inborn errors of metabolism. Genet. Med. 21, 102–106 (2019).

    Article  PubMed  Google Scholar 

  129. Keating, S. T., van Diepen, J. A., Riksen, N. P. & El-Osta, A. Epigenetics in diabetic nephropathy, immunity and metabolism. Diabetologia 61, 6–20 (2018).

    Article  CAS  PubMed  Google Scholar 

  130. Osuna-Prieto, F. J. et al. Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults. Cardiovasc. Diabetol. 20, 151 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Prag, H. A. et al. Mechanism of succinate efflux upon reperfusion of the ischaemic heart. Cardiovasc. Res. 117, 1188–1201 (2021).

    Article  CAS  PubMed  Google Scholar 

  132. Reddy, A. et al. pH-Gated succinate secretion regulates muscle remodeling in response to exercise. Cell 183, 62–75.e17 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Valentova, M., Anker, S. D. & von Haehling, S. Cardiac cachexia revisited: the role of wasting in heart failure. Heart Fail. Clin. 16, 61–69 (2020).

    Article  PubMed  Google Scholar 

  134. von Haehling, S. & Anker, S. D. Cachexia as a major underestimated and unmet medical need: facts and numbers. J. Cachexia Sarcopenia Muscle 1, 1–5 (2010).

    Article  Google Scholar 

  135. Palenik, C. J. & Miller, C. H. Treating highly infectious patients in the dental office. J. Indiana Dent. Assoc. 64, 11–15 (1985).

    CAS  PubMed  Google Scholar 

  136. Argiles, J. M., Busquets, S., Stemmler, B. & Lopez-Soriano, F. J. Cancer cachexia: understanding the molecular basis. Nat. Rev. Cancer 14, 754–762 (2014).

    Article  CAS  PubMed  Google Scholar 

  137. Baazim, H., Antonio-Herrera, L. & Bergthaler, A. The interplay of immunology and cachexia in infection and cancer. Nat. Rev. Immunol. https://doi.org/10.1038/s41577-021-00624-w (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Ling, H. H. et al. Clinical significance of serum glutamine level in patients with colorectal cancer. Nutrients 11, 898 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  139. Katt, W. P., Antonyak, M. A. & Cerione, R. A. Simultaneously and kidney type glutaminase sensitizes cancer cells to acid toxicity and offers new opportunities for therapeutic intervention. Mol. Pharm. 12, 46–55 (2015).

    Article  CAS  PubMed  Google Scholar 

  140. Garcia-Bermudez, J. et al. Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. Nat. Cell Biol. 20, 775–781 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Moslehi, J., Lichtman, A. H., Sharpe, A. H., Galluzzi, L. & Kitsis, R. N. Immune checkpoint inhibitor-associated myocarditis: manifestations and mechanisms. J. Clin. Invest. 131, e145186 (2021).

    Article  CAS  PubMed Central  Google Scholar 

  142. Li, W. et al. Cardiovascular and thrombotic complications of novel multiple myeloma therapies: a review. JAMA Oncol. 3, 980–988 (2017).

    Article  PubMed  Google Scholar 

  143. Li, W. et al. Vascular and metabolic implications of novel targeted cancer therapies: focus on kinase inhibitors. J. Am. Coll. Cardiol. 66, 1160–1178 (2015).

    Article  PubMed  Google Scholar 

  144. Sheng, C. C. et al. 21st century cardio-oncology: identifying cardiac safety signals in the era of personalized medicine. JACC Basic. Transl. Sci. 1, 386–398 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Spetz, J., Moslehi, J. & Sarosiek, K. Radiation-induced cardiovascular toxicity: mechanisms, prevention, and treatment. Curr. Treat. Options Cardiovasc. Med. 20, 31 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Suliman, H. B. et al. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J. Clin. Invest. 117, 3730–3741 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Leite de Oliveira, R. et al. Gene-targeting of Phd2 improves tumor response to chemotherapy and prevents side-toxicity. Cancer Cell 22, 263–277 (2012).

    Article  CAS  PubMed  Google Scholar 

  148. Campia, U. et al. Cardio-oncology: vascular and metabolic perspectives: a scientific statement from the American Heart Association. Circulation 139, e579–e602 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Hu, J. R. et al. Cardiovascular effects of androgen deprivation therapy in prostate cancer contemporary meta-analyses. Arterioscler. Thromb. Vasc. Biol. 40, e55–e64 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Cohen, P., Cross, D. & Janne, P. A. Kinase drug discovery 20 years after imatinib: progress and future directions. Nat. Rev. Drug Discov. 20, 551–569 (2021).

    Article  CAS  PubMed  Google Scholar 

  151. Motzer, R. J. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115–124 (2007).

    Article  CAS  PubMed  Google Scholar 

  152. Rini, B. I. et al. Prospective cardiovascular surveillance of immune checkpoint inhibitor-based combination therapy in patients with advanced renal cell cancer: data from the phase III JAVELIN renal 101 trial. J. Clin. Oncol. https://doi.org/10.1200/JCO.21.01806 (2022).

    Article  PubMed  Google Scholar 

  153. Nazer, B., Humphreys, B. D. & Moslehi, J. Effects of novel angiogenesis inhibitors for the treatment of cancer on the cardiovascular system: focus on hypertension. Circulation 124, 1687–1691 (2011).

    Article  PubMed  Google Scholar 

  154. Richards, C. J. et al. Incidence and risk of congestive heart failure in patients with renal and nonrenal cell carcinoma treated with sunitinib. J. Clin. Oncol. 29, 3450–3456 (2011).

    Article  CAS  PubMed  Google Scholar 

  155. Bair, S. M., Choueiri, T. K. & Moslehi, J. Cardiovascular complications associated with novel angiogenesis inhibitors: emerging evidence and evolving perspectives. Trends Cardiovasc. Med. 23, 104–113 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Giordano, F. J. et al. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc. Natl Acad. Sci. USA 98, 5780–5785 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Lee, Y. et al. Life-threatening hypoglycemia induced by a tyrosine kinase inhibitor in a patient with neuroendocrine tumor: a case report. Diabetes Res. Clin. Pract. 93, e68–e70 (2011).

    Article  PubMed  Google Scholar 

  158. Louvet, C. et al. Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc. Natl Acad. Sci. USA 105, 18895–18900 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Villalta, S. A. et al. Inhibition of VEGFR-2 reverses type 1 diabetes in NOD mice by abrogating insulitis and restoring islet function. Diabetes 62, 2870–2878 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Hamberg, P. et al. Non-islet-cell tumor induced hypoglycemia in patients with advanced gastrointestinal stromal tumor possibly worsened by imatinib. J. Clin. Oncol. 24, e30–e31 (2006).

    Article  PubMed  Google Scholar 

  161. Barber, M. C., Mauro, M. J. & Moslehi, J. Cardiovascular care of patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) therapy. Hematol. Am. Soc. Hematol. Educ. Program. 2017, 110–114 (2017).

    Article  Google Scholar 

  162. Manouchehri, A. et al. Tyrosine kinase inhibitors in leukemia and cardiovascular events: from mechanism to patient care. Arterioscler. Thromb. Vasc. Biol. 40, 301–308 (2020).

    Article  CAS  PubMed  Google Scholar 

  163. Moslehi, J. J. & Deininger, M. Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J. Clin. Oncol. 33, 4210–4218 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Veneri, D., Franchini, M. & Bonora, E. Imatinib and regression of type 2 diabetes. N. Engl. J. Med. 352, 1049–1050 (2005).

    Article  CAS  PubMed  Google Scholar 

  165. Uraizee, I., Cheng, S. & Moslehi, J. Reversible cardiomyopathy associated with sunitinib and sorafenib. N. Engl. J. Med. 365, 1649–1650 (2011).

    Article  CAS  PubMed  Google Scholar 

  166. Chintalgattu, V. et al. Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity. Sci. Transl. Med. 5, 187ra169 (2013).

    Article  CAS  Google Scholar 

  167. May, D. et al. Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc. Natl Acad. Sci. USA 105, 282–287 (2008).

    Article  CAS  PubMed  Google Scholar 

  168. Moslehi, J. et al. Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation 122, 1004–1016 (2010).

    Article  CAS  PubMed  Google Scholar 

  169. Bekeredjian, R. et al. Conditional HIF-1α expression produces a reversible cardiomyopathy. PLoS ONE 5, e11693 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Yen, K. et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discov. 7, 478–493 (2017).

    Article  CAS  PubMed  Google Scholar 

  171. DiNardo, C. D. et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N. Engl. J. Med. 378, 2386–2398 (2018).

    Article  CAS  PubMed  Google Scholar 

  172. Gatto, L. et al. IDH inhibitors and beyond: the cornerstone of targeted glioma treatment. Mol. Diagn. Ther. 25, 457–473 (2021).

    Article  CAS  PubMed  Google Scholar 

  173. Kam, A. E., Masood, A. & Shroff, R. T. Current and emerging therapies for advanced biliary tract cancers. Lancet Gastroenterol. Hepatol. 6, 956–969 (2021).

    Article  PubMed  Google Scholar 

  174. Norsworthy, K. J. et al. FDA approval summary: ivosidenib for relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation. Clin. Cancer Res. 25, 3205–3209 (2019).

    Article  CAS  PubMed  Google Scholar 

  175. Baik, A. H. et al. Mechanisms of cardiovascular toxicities associated with immunotherapies. Circ. Res. 128, 1780–1801 (2021).

    Article  CAS  PubMed  Google Scholar 

  176. Lehmann, L. H. et al. Clinical strategy for the diagnosis and treatment of immune checkpoint inhibitor-associated myocarditis: a narrative review. JAMA Cardiol. 6, 1329–1337 (2021).

    Article  PubMed  Google Scholar 

  177. Johnson, D. B. et al. Immune checkpoint inhibitor toxicities: systems-based approaches to improve patient care and research. Lancet Oncol. 21, e398–e404 (2020).

    Article  CAS  PubMed  Google Scholar 

  178. Hu, J. R. et al. High sensitivity troponin T and NT-proBNP in patients receiving chimeric antigen receptor (CAR) T-cell therapy. Clin. Hematol. Int. 3, 96–102 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Dolladille, C. et al. Chimeric antigen receptor T-cells safety: a pharmacovigilance and meta-analysis study. Am. J. Hematol. 96, 1101–1111 (2021).

    Article  CAS  PubMed  Google Scholar 

  180. Salem, J. E., Ederhy, S., Lebrun-Vignes, B. & Moslehi, J. J. Cardiac events associated with chimeric antigen receptor T-cells (CAR-T): a VigiBase perspective. J. Am. Coll. Cardiol. 75, 2521–2523 (2020).

    Article  CAS  PubMed  Google Scholar 

  181. Abou-Alfa, G. K. et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21, 796–807 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Tap, W. D. et al. Phase I study of the mutant IDH1 inhibitor ivosidenib: safety and clinical activity in patients with advanced chondrosarcoma. J. Clin. Oncol. 38, 1693–1701 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Descamps, O., Riondel, J., Ducros, V. & Roussel, A. M. Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech. Ageing Dev. 126, 1185–1191 (2005).

    Article  CAS  PubMed  Google Scholar 

  184. Berrigan, D., Perkins, S. N., Haines, D. C. & Hursting, S. D. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis 23, 817–822 (2002).

    Article  CAS  PubMed  Google Scholar 

  185. Mattson, M. P., Longo, V. D. & Harvie, M. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 39, 46–58 (2017).

    Article  PubMed  Google Scholar 

  186. Longo, V. D. & Mattson, M. P. Fasting: molecular mechanisms and clinical applications. Cell Metab. 19, 181–192 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. de Cabo, R. & Mattson, M. P. Effects of intermittent fasting on health, aging, and disease. N. Engl. J. Med. 381, 2541–2551 (2019).

    Article  PubMed  Google Scholar 

  188. Lien, E. C. et al. Low glycaemic diets alter lipid metabolism to influence tumour growth. Nature 599, 302–307 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Stroud, A. M. et al. Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort. Surg. Obes. Relat. Dis. 16, 1086–1094 (2020).

    Article  PubMed  Google Scholar 

  190. Dale, K. M., Coleman, C. I., Henyan, N. N., Kluger, J. & White, C. M. Statins and cancer risk: a meta-analysis. JAMA 295, 74–80 (2006).

    Article  CAS  PubMed  Google Scholar 

  191. Rugo, H. S. et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann. Oncol. 31, 1001–1010 (2020).

    Article  CAS  PubMed  Google Scholar 

  192. Andre, F. et al. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann. Oncol. 32, 208–217 (2021).

    Article  CAS  PubMed  Google Scholar 

  193. Ferraro, G. B. et al. Fatty acid synthesis is required for breast cancer brain metastasis. Nat. Cancer 2, 414–428 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Wei, X. et al. Targeting ACLY attenuates tumor growth and acquired cisplatin resistance in ovarian cancer by inhibiting the PI3K-AKT pathway and activating the AMPK-ROS pathway. Front. Oncol. 11, 642229 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  195. Xin, M. et al. miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer. Oncotarget 7, 44252–44265 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Tracz-Gaszewska, Z. & Dobrzyn, P. Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers 11, 948 (2019).

    Article  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

A.K. is supported by NIH award R00-HL-1417. J.M. is supported by NIH grants R01HL141466, R01HL155990 and R01HL156021. R.A.d.B. is supported by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF) and by grants from the Netherlands Heart Foundation (grants 2017-21; 2017-11; 2018-30; 2020B005).

Author information

Authors and Affiliations

  1. Department of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Anja Karlstaedt

  2. Section of Cardio-Oncology & Immunology, Division of Cardiology and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

    Javid Moslehi

  3. Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands

    Rudolf A. de Boer

Authors
  1. Anja Karlstaedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Javid Moslehi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rudolf A. de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed substantially to all aspects of the article.

Corresponding authors

Correspondence to Javid Moslehi or Rudolf A. de Boer.

Ethics declarations

Competing interests

J.M. has served on advisory boards for Amgen, AstraZeneca, Audentes, Boston Biomedical, Bristol Myers Squibb, Cytokinetics, Deciphera, Immunocore, Ipsen, Janssen, Myovant, Precigen Triple-Gene, Regeneron and Takeda. R.A.d.B. reports research grants from Abbott, AstraZeneca, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk and Roche; and reports speaker fees from Abbott, AstraZeneca, Bayer, Novartis and Roche. A.K. declares no competing interests.

Peer review

Peer review information

Nature Reviews Cardiology thanks Dimitrios Farmakis, Giorgio Minotti and Radek Pudil for their contribution to the peer review of this work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karlstaedt, A., Moslehi, J. & de Boer, R.A. Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer. Nat Rev Cardiol 19, 414–425 (2022). https://doi.org/10.1038/s41569-022-00698-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41569-022-00698-6

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing