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PI3K signalling at the intersection of cardio-oncology networks: cardiac safety in the era of AI

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Abstract

Class I phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases. They are super elevated in many human cancer types and exert their main cellular functions by activating Akt to trigger an array of distinct responses, affecting metabolism and cell polarity. The signal equally plays important roles in cardiovascular pathophysiology. PI3K is required for cardiogenesis and regulation of cardiac structure and function. Overexpression of PI3K governs the development of cardiac pressure overload adaptation and compensatory hypertrophy. Therefore, inhibition of PI3K shortens life span, enhances cardiac dysfunction and pathological hypertrophy. The inverse inhibition effect, however, desirably destroys many cancer cells by blocking several aspects of the tumorigenesis phenotype. Given the contrasting effects in cardio-oncology; the best therapeutic strategy to target PI3K in cancer, while maintaining or rather increasing cardiac safety is under intense investigational scrutiny. To improve our molecular understanding towards identifying cardiac safety signalling of PI3K and/or better therapeutic strategy for cancer treatment, this article reviews PI3K signalling in cardio-oncology. PI3K signalling at the interface of metabolism, inflammation and immunity, and autonomic innervation networks were examined. Examples were then given of cardiovascular drugs that target the networks, being repurposed for cancer treatment. This was followed by an intersection scheme of the networks that can be functionalised with machine learning for safety and risk prediction, diagnoses, and defining new novel encouraging leads and targets for clinical translation. This will hopefully overcome the challenges of the one-signalling-one-health-outcome alliance, and expand our knowledge of the totality of PI3K signalling in cardio-oncology.

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References

  1. Auger KR, Serunian LA, Soltoff SP, Libby P, Cantley LC (1989) PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57(1):167–175

    Article  CAS  Google Scholar 

  2. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    Article  CAS  Google Scholar 

  3. Oeing CU, Jun S, Mishra S, Dunkerly-Eyring B, Chen A, Grajeda MI et al (2021) MTORC1-regulated metabolism controlled by TSC2 limits cardiac reperfusion injury. Circ Res. https://doi.org/10.1161/CIRCRESAHA.120.317710

    Article  Google Scholar 

  4. Pfefferli C, Bonvin M, Robatel S, Perler J, König D, Jaźwińska A (2020) Oncogeneinduced cardiac neoplasia shares similar mechanisms with heart regeneration in zebrafish. https://doi.org/10.1101/2020.12.15.422853

  5. Butcher JT, Norris RA, Hoffman S, Mjaatvedt CH, Markwald RR (2007) Periostin promotes atrioventricular mesenchyme matrix invasion and remodeling mediated by integrin signaling through Rho/PI 3-kinase. Dev Biol 302(1):256–266

    Article  CAS  Google Scholar 

  6. Kuhn B, del Monte F, Hajjar RJ, Chang YS, Lebeche D, Arab S et al (2007) Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat Med 13(8):962–969

    Article  Google Scholar 

  7. Bi L, Okabe I, Bernard DJ, Wynshaw-Boris A, Nussbaum RL (1999) Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem 274(16):10963–10968

    Article  CAS  Google Scholar 

  8. Lin RC, Weeks KL, Gao XM, Williams RB, Bernardo BC, Kiriazis H et al (2010) PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA. Arterioscler Thromb Vasc Biol 30(4):724–732

    Article  CAS  Google Scholar 

  9. McMullen JR, Amirahmadi F, Woodcock EA, Schinke-Braun M, Bouwman RD, Hewitt KA et al (2007) Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A 104(2):612–617

    Article  CAS  Google Scholar 

  10. Polina I, Jansen HJ, Li T, Moghtadaei M, Bohne LJ, Liu Y et al (2020) Loss of insulin signaling may contribute to atrial fibrillation and atrial electrical remodeling in type 1 diabetes. Proc Natl Acad Sci USA 117(14):7990–8000

    Article  CAS  Google Scholar 

  11. Ezeani M, Elom S (2017) Necessity to evaluate PI3K/Akt signalling pathway in proarrhythmia. Open Heart 4(2):e000596

    Article  Google Scholar 

  12. Ezeani M, Prabhu S (2021) Pathophysiology and therapeutic relevance of PI3K(p110alpha) protein in atrial fibrillation: A non-interventional molecular therapy strategy. Pharmacol Res 165:105415

    Article  CAS  Google Scholar 

  13. Bluethmann SM, Mariotto AB, Rowland JH (2016) Anticipating the “Silver Tsunami”: prevalence trajectories and comorbidity burden among older cancer survivors in the United States. Cancer Epidemiol Biomarkers Prev 25(7):1029–1036

    Article  Google Scholar 

  14. Asnani A (2021) Preclinical models of cancer therapy-associated cardiovascular toxicity a scientific statement from the American Heart Association. Circ Res. https://doi.org/10.1161/RES.0000000000000473

    Article  Google Scholar 

  15. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B (2010) The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol 11(5):329–341

    Article  CAS  Google Scholar 

  16. Foster JG, Blunt MD, Carter E, Ward SG (2012) Inhibition of PI3K signaling spurs new therapeutic opportunities in inflammatory/autoimmune diseases and hematological malignancies. Pharmacol Rev 64(4):1027–1054

    Article  CAS  Google Scholar 

  17. Okkenhaug K (2013) Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol 31:675–704

    Article  CAS  Google Scholar 

  18. Damilano F, Franco I, Perrino C, Schaefer K, Azzolino O, Carnevale D et al (2011) Distinct effects of leukocyte and cardiac phosphoinositide 3-kinase gamma activity in pressure overload-induced cardiac failure. Circulation 123(4):391–399

    Article  CAS  Google Scholar 

  19. Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG et al (2011) Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell 19(6):715–727

    Article  CAS  Google Scholar 

  20. Hawkins PT, Stephens LR (2015) PI3K signalling in inflammation. Biochim Biophys Acta 1851(6):882–897

    Article  CAS  Google Scholar 

  21. Gao X, Lowry PR, Zhou X, Depry C, Wei Z, Wong GW et al (2011) PI3K/Akt signaling requires spatial compartmentalization in plasma membrane microdomains. Proc Natl Acad Sci USA 108(35):14509–14514

    Article  CAS  Google Scholar 

  22. Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM et al (2008) Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol 4(9):538–547

    Article  CAS  Google Scholar 

  23. Lal H, Ahmad F, Woodgett J, Force T (2015) The GSK-3 family as therapeutic target for myocardial diseases. Circ Res 116(1):138–149

    Article  CAS  Google Scholar 

  24. Ranek MJ, Kokkonen-Simon KM, Chen A, Dunkerly-Eyring BL, Vera MP, Oeing CU et al (2019) PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress. Nature 566(7743):264–269

    Article  CAS  Google Scholar 

  25. Patel TB (2004) Single transmembrane spanning heterotrimeric g protein-coupled receptors and their signaling cascades. Pharmacol Rev 56(3):371–385

    Article  CAS  Google Scholar 

  26. Dreyling M, Santoro A, Mollica L, Leppa S, Follows GA, Lenz G et al (2017) Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol 35(35):3898–3905

    Article  CAS  Google Scholar 

  27. Patnaik A, Appleman LJ, Tolcher AW, Papadopoulos KP, Beeram M, Rasco DW et al (2016) First-in-human phase I study of copanlisib (BAY 80–6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin’s lymphomas. Ann Oncol 27(10):1928–1940

    Article  CAS  Google Scholar 

  28. Xu K, Yin N, Peng M, Stamatiades EG, Shyu A, Li P et al (2021) Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity. Science 371(6527):405–410

    Article  CAS  Google Scholar 

  29. Boudina S, Abel ED (2006) Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda) 21:250–258

    CAS  Google Scholar 

  30. Boudina S, Abel ED (2007) Diabetic cardiomyopathy revisited. Circulation 115(25):3213–3223

    Article  Google Scholar 

  31. Damaghia M (2021) The harsh microenvironment in early breast cancer selects for a Warburg phenotype. PNAS. https://doi.org/10.1073/pnas.2011342118

    Article  Google Scholar 

  32. Boudina S, Sena S, O’Neill BT, Tathireddy P, Young ME, Abel ED (2005) Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112(17):2686–2695

    Article  Google Scholar 

  33. Rees ML, Subramaniam J, Li Y, Hamilton DJ, Frazier OH, Taegtmeyer H (2015) A PKM2 signature in the failing heart. Biochem Biophys Res Commun 459(3):430–436

    Article  CAS  Google Scholar 

  34. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3(3):187–197

    Article  CAS  Google Scholar 

  35. Sutendra G, Dromparis P, Kinnaird A, Stenson TH, Haromy A, Parker JM et al (2013) Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer. Oncogene 32(13):1638–1650

    Article  CAS  Google Scholar 

  36. Krishnan J, Suter M, Windak R, Krebs T, Felley A, Montessuit C et al (2009) Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy. Cell Metab 9(6):512–524

    Article  CAS  Google Scholar 

  37. Zhou M, Xu X, Wang H, Yang G, Yang M, Zhao X et al (2020) Effect of central JAZF1 on glucose production is regulated by the PI3K-Akt-AMPK pathway. FASEB J 34(5):7058–7074

    Article  CAS  Google Scholar 

  38. Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L et al (2022) Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. J Clin Invest. https://doi.org/10.1172/JCI153724

    Article  Google Scholar 

  39. Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S et al (2014) A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med 370(20):1909–1919

    Article  Google Scholar 

  40. Becker W (2018) A wake-up call to quiescent cancer cells - potential use of DYRK1B inhibitors in cancer therapy. FEBS J 285(7):1203–1211

    Article  CAS  Google Scholar 

  41. Adamo L, Rocha-Resende C, Prabhu SD, Mann DL (2020) Reappraising the role of inflammation in heart failure. Nat Rev Cardiol 17(5):269–285

    Article  Google Scholar 

  42. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899

    Article  CAS  Google Scholar 

  43. Koyasu S (2003) The role of PI3K in immune cells. Nat Immunol 4(4):313–319

    Article  CAS  Google Scholar 

  44. Kerr WG, Chisholm JD (2019) The next generation of immunotherapy for cancer: small molecules could make big waves. J Immunol 202(1):11–19

    Article  CAS  Google Scholar 

  45. Medzhitov R, Horng T (2009) Transcriptional control of the inflammatory response. Nat Rev Immunol 9(10):692–703

    Article  CAS  Google Scholar 

  46. Mann DL (2011) The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circ Res 108(9):1133–1145

    Article  CAS  Google Scholar 

  47. Pourrajab F, Yazdi MB, Zarch MB, Zarch MB, Hekmatimoghaddam S (2015) Cross talk of the first-line defense TLRs with PI3K/Akt pathway, in preconditioning therapeutic approach. Mol Cell Ther 3:4

    Article  Google Scholar 

  48. Chen E, Chen C, Niu Z, Gan L, Wang Q, Li M et al (2020) Poly(I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway. Signal Transduct Target Ther 5(1):216

    Article  CAS  Google Scholar 

  49. Al-Huseini I, Harada M, Nishi K, Nguyen-Tien D, Kimura T, Ashida N (2019) Improvement of insulin signalling rescues inflammatory cardiac dysfunction. Sci Rep 9(1):14801

    Article  Google Scholar 

  50. Silva MC, Davoli-Ferreira M, Medina TS, Sesti-Costa R, Silva GK, Lopes CD et al (2018) Canonical PI3Kgamma signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis. Nat Commun 9(1):1513

    Article  Google Scholar 

  51. Patrucco E, Notte A, Barberis L, Selvetella G, Maffei A, Brancaccio M et al (2004) PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell 118(3):375–387

    Article  CAS  Google Scholar 

  52. Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S et al (2016) PI3Kgamma is a molecular switch that controls immune suppression. Nature 539(7629):437–442

    Article  CAS  Google Scholar 

  53. Levy MN (1971) Sympathetic-parasympathetic interactions in the heart. Circ Res 29(5):437–445

    Article  CAS  Google Scholar 

  54. Harvey W (1929) Exercitatio anatomica de Motu Cordis et Sanguinis in animalibus. Charles C Thomas, Springfield

    Book  Google Scholar 

  55. Herring N, Kalla M, Paterson DJ (2019) The autonomic nervous system and cardiac arrhythmias: current concepts and emerging therapies. Nat Rev Cardiol 16(12):707–726

    Article  Google Scholar 

  56. Kamiya A, Hayama Y, Kato S, Shimomura A, Shimomura T, Irie K et al (2019) Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression. Nat Neurosci 22(8):1289–1305

    Article  CAS  Google Scholar 

  57. Zahalka AH, Frenette PS (2020) Nerves in cancer. Nat Rev Cancer 20(3):143–157

    Article  CAS  Google Scholar 

  58. Badoer E (2001) Hypothalamic paraventricular nucleus and cardiovascular regulation. Clin Exp Pharmacol Physiol 28(1–2):95–99

    Article  CAS  Google Scholar 

  59. Fan ZD (2012) Artificial microRNA interference targeting AT(1a) receptors in paraventricular nucleus attenuates hypertension in rats. Gene Ther 19:810–817

    Article  CAS  Google Scholar 

  60. Shi Y, Yin J, Hu H, Xue M, Li X, Liu J et al (2019) Targeted regulation of sympathetic activity in paraventricular nucleus reduces inducible ventricular arrhythmias in rats after myocardial infarction. J Cardiol 73(1):81–88

    Article  Google Scholar 

  61. Lagadec C, Meignan S, Adriaenssens E, Foveau B, Vanhecke E, Romon R et al (2009) TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 28(18):1960–1970

    Article  CAS  Google Scholar 

  62. Renz BW, Takahashi R, Tanaka T, Macchini M, Hayakawa Y, Dantes Z et al (2018) beta2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer. Cancer Cell 34(5):863–867

    Article  CAS  Google Scholar 

  63. Tang J, Li Z, Lu L, Cho CH (2021) Beta-Adrenergic system, a backstage manipulator regulating tumour progression and drug target in cancer therapy. Semin Cancer Biol 23(6):533–542

    Article  Google Scholar 

  64. Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C et al (2006) Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 12(8):939–944

    Article  CAS  Google Scholar 

  65. Weddle DL, Tithoff P, Williams M, Schuller HM (2001) Beta-adrenergic growth regulation of human cancer cell lines derived from pancreatic ductal carcinomas. Carcinogenesis 22(3):473–479

    Article  CAS  Google Scholar 

  66. Zenewicz LA (2017) Oxygen levels and immunological studies. Front Immunol 8:324

    Article  Google Scholar 

  67. Myers MG Jr, Olson DP (2012) Central nervous system control of metabolism. Nature 491(7424):357–363

    Article  CAS  Google Scholar 

  68. Nishida K, Otsu K (2017) Inflammation and metabolic cardiomyopathy. Cardiovasc Res 113(4):389–398

    Article  CAS  Google Scholar 

  69. Hoxhaj G, Manning BD (2020) The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer 20(2):74–88

    Article  CAS  Google Scholar 

  70. Espinoza L, Fedorchak S, Boychuk CR (2021) Interplay between systemic metabolic cues and autonomic output: connecting cardiometabolic function and parasympathetic circuits. Front Physiol 12:624595

    Article  Google Scholar 

  71. Zahalka AH, Arnal-Estape A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS et al (2017) Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science 358(6361):321–326

    Article  CAS  Google Scholar 

  72. Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ (2003) The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 9(5–8):125–134

    Article  CAS  Google Scholar 

  73. Pavlov VA, Tracey KJ (2017) Neural regulation of immunity: molecular mechanisms and clinical translation. Nat Neurosci 20(2):156–166

    Article  CAS  Google Scholar 

  74. Wang B, Wu L, Chen J, Dong L, Chen C, Wen Z et al (2021) Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduct Target Ther 6(1):94

    Article  CAS  Google Scholar 

  75. Sheng CC, Amiri-Kordestani L, Palmby T, Force T, Hong CC, Wu JC et al (2016) 21st century cardio-oncology: identifying cardiac safety signals in the era of personalized medicine. JACC Basic Transl Sci 1(5):386–398

    Article  Google Scholar 

  76. Lin DC, Xu L, Ding LW, Sharma A, Liu LZ, Yang H et al (2013) Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancers. Proc Natl Acad Sci USA 110(15):6109–6114

    Article  CAS  Google Scholar 

  77. Karam S, Margaria JP, Bourcier A, Mika D, Varin A, Bedioune I et al (2020) Cardiac Overexpression of PDE4B Blunts beta-Adrenergic Response and Maladaptive Remodeling in Heart Failure. Circulation 142(2):161–174

    Article  CAS  Google Scholar 

  78. Rhee J (2015) The role of GAPDH in the cardio-metabolic response to ischemia. Circ Res 117:A386

    Article  Google Scholar 

  79. Liberti MV, Dai Z, Wardell SE, Baccile JA, Liu X, Gao X et al (2017) A predictive model for selective targeting of the Warburg effect through GAPDH inhibition with a natural product. Cell Metab 26(4):648–659

    Article  CAS  Google Scholar 

  80. Yang C, Liu T, Shi GP (2020) Therapeutic potential of tricarboxylic acid cycle metabolite itaconate in cardiovascular diseases. EBioMedicine 59:102938

    Article  CAS  Google Scholar 

  81. Cardenas C, Lovy A, Silva-Pavez E, Urra F, Mizzoni C, Ahumada-Castro U et al (2020) Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca(2+) transfer for survival. Sci Signal. 13(640):eaay1212

    Article  CAS  Google Scholar 

  82. Paillard M, Tubbs E, Thiebaut PA, Gomez L, Fauconnier J, Da Silva CC et al (2013) Depressing mitochondria-reticulum interactions protects cardiomyocytes from lethal hypoxia-reoxygenation injury. Circulation 128(14):1555–1565

    Article  CAS  Google Scholar 

  83. Madsen RR, Vanhaesebroeck B (2020) Cracking the context-specific PI3K signaling code. Sci Signal 13(613):eaay2940

    Article  CAS  Google Scholar 

  84. Lu MY, Chen TY, Williamson DFK, Zhao M, Shady M, Lipkova J et al (2021) AI-based pathology predicts origins for cancers of unknown primary. Nature 594:106–110

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge the help and support of Professor Christoph Hagemeyer during the time of the study.

Funding

ME is supported by Government of Australia Training Research Program Scholarship and Monash University, Faculty of Medicine, Nursing and Health Sciences Postgraduate Excellence Award. SP is supported by National Health and Medical Research Council Emerging Leader Fellowship, and Heart Foundation Post-Doctoral Fellowship.

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  1. NanoBiotechnology Laboratory, Australian Centre for Blood Diseases, Faculty of Medicine, Nursing and Health Sciences, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia

    Martin Ezeani

  2. The Alfred, and University of Melbourne, Parkville, Melbourne, VIC, 3010, Australia

    Sandeep Prabhu

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  1. Martin Ezeani
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ME conceived the idea and developed concepts, performed research and collated literature, wrote and edited the paper. SP wrote and edited the paper.

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Correspondence to Martin Ezeani.

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Ezeani, M., Prabhu, S. PI3K signalling at the intersection of cardio-oncology networks: cardiac safety in the era of AI. Cell. Mol. Life Sci. 79, 594 (2022). https://doi.org/10.1007/s00018-022-04627-1

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