Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost

Figures

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  Figure 1. Mechanisms of cardioprotection that present a possible crosstalk with anticancer therapies. Summary of cardiotoxic mechanisms of VEGF, Immune Checkpoint and Proteasome Inhibitors. Arrows correspond to downstream activation and blunt lines to inhibitory effect, green arrows correspond to positive effects, red arrows correspond to negative effects. A Gene, Apoptotic Gene; AA gene, Anti-apoptotic Gene; Akt, Protein kinase B; eNOS, endothelial nitric oxide synthase; Src, Proto-oncogene tyrosine-protein kinase; ERK 1/2, Extracellular signal-regulated kinases; FAK, Focal adhesion kinase; IFNγ, interferon gamma; IKKa, inhibitor of nuclear factor kappa-B kinase subunit alpha; LC3B, Microtubule-associated protein 1A/1B-light chain 3; MEK, Mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Raptor, Regulatory-associated protein of mTOR; PI3K, Phosphoinositide 3-kinase; PKC, protein kinase C; PP2A, protein phosphatase 2A; Raf, Serine/threonine-protein kinase; STAT1 or 3, Signal Transducer And Activator Of Transcription 1 or 3. Figure was constructed using images from Servier Medical Art by…

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  Figure 2. Crosstalk between VEGF/VEGFR inhibitors and cardioprotection. VEGF or VEGFR blockade inhibits Reperfusion Injury Salvage Kinase (RISK) and PKC signaling, both activated by Ischemic Conditioning, therefore diminishing endogenous cardioprotection. Arrows correspond to downstream activation and green arrows correspond to positive effects. Akt, Protein kinase B; eNOS, endothelial nitric oxide synthase; Src, Proto-oncogene tyrosine-protein kinase; ERK 1/2, Extracellular signal-regulated kinases; FAK, Focal adhesion kinase; MEK, Mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; PI3K, Phosphoinositide 3-kinase; PKC, protein kinase C; Raf, Serine/threonine-protein kinase; STAT3, Signal Transducer And Activator Of Transcription 3. Figure was constructed using images from Servier Medical Art by Servier.

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  Figure 3. Crosstalk between proteasome inhibitors and cardioprotection. Proteasome inhibitors either by NFκΒ activation or by a PP2A-dependent abrogation of Reperfusion Injury Salvage Kinase (RISK) pathway interfere with endogenous cardioprotective mechanisms. Arrows correspond to downstream activation and blunt lines to inhibitory effect, green arrows correspond to positive effects, and red arrows correspond to negative effects. A Gene, Apoptotic Gene; Akt, Protein kinase B; eNOS, endothelial nitric oxide synthase; ERK 1/2, Extracellular signal-regulated kinases; IKKa, inhibitor of nuclear factor kappa-B kinase subunit alpha; LC3B, Microtubule-associated protein 1A/1B-light chain 3B; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Raptor, Regulatory-associated protein of mTOR; PI3K, Phosphoinositide 3-kinase; PP2A, protein phosphatase 2A. Figure was constructed using images from Servier Medical Art by Servier.

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  Figure 4. Hypothesized crosstalk between Immune Checkpoint inhibitors and cardioprotection. IFNγR and TNFR signaling is hypothesized to abrogate endogenous cardioprotective mechanisms. Implications of overt inflammation in the myocardium. Arrows correspond to downstream activation and red arrows correspond to negative effects. A Gene, Apoptotic Gene; AA gene, Anti-apoptotic Gene; Akt, Protein kinase B; ERK 1/2, Extracellular signal-regulated kinases; IFNγ, interferon gamma; IKKa, inhibitor of nuclear factor kappa-B kinase subunit alpha; MEK, Mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; Raptor, Regulatory-associated protein of mTOR; PI3K, Phosphoinositide 3-kinase; PKC, protein kinase C; Raf, Serine/threonine-protein kinase; STAT1 or 3, Signal Transducer And Activator Of Transcription 1 or 3. Figure was constructed using images from Servier Medical Art by Servier.