Diabetic Retinopathy and Ocular Melanoma: How Far We Are?
Abstract
:1. Introduction
2. Angiogenesis and Anti-Angiogenic Therapy
3. Diabetic Retinopathy, Angiogenesis and Anti-Angiogenic Therapy
4. Uveal Melanoma, Angiogenesis and Anti-Angiogenic Therapy
5. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AMD | Age-related macular degeneration |
Ang-2 | Angiopoietin-2 |
bFGF | basic fibroblast growth factor |
BRB | Blood-retinal barriers |
CNV | Choroidal neovascularization |
DME | Diabetic macular edema |
DR | Diabetic retinopathy |
GFAP | Glial fibrillary acidic protein |
HMGB1 | High mobility group protein B1 |
HOS | Hyperosmolar stress |
IGF-1R | Insulin growth factor- 1 receptor |
IL | Interleukins |
IL6 | Interleukin 6 |
IL8 | Interleukin 8 |
MCP-1 | Monocyte chemoattractant protein-1 |
MGCs | Müller glial cells |
MGSA | Melanoma growth stimulatory activity |
MIP1 | Macrophage inflammatory protein 1 |
MMPs | Matrix metalloproteinases |
NAP2 | Neutrophil activating protein 2 |
NFAT5 | Nuclear factor of activated T-cells 5 |
NPDR | Non-proliferative DR |
PDGF | Platelet-derived growth factor-BB |
PDR | Proliferation DR |
PIGF | Placental growth factor |
RGCs | Retinal ganglion cells |
ROS | Reactive oxygen species |
RPE | Retinal pigmented epithelial cells |
RT | Radiotherapy |
SOD | Superoxide dismutase |
TLRs | Toll-like receptors |
TNFα | Tumour necrosis alpha |
TonEBP | Transcription factor tonicity-responsive binding-protein |
UV | Ultraviolet |
VEGF | Vascular endothelial growth factor |
VEGR | Vascular endothelial growth receptor |
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Drug | Studies/Observations |
---|---|
Bevacizumab | Yang et al. proved that in ocular melanoma bevacizumab allows suppression of primary tumour growth, reduction of liver micrometastases and decreased VEGF levels [162]. Filali et al. observed that in vitro uveal melanoma cell proliferation did not occur, but in vivo, the use of bevacizumab caused greater intraocular tumour growth, especially under hypoxic conditions. With treatment, anterior chamber and tumour bleedings were observed in the eyes, increasing microvascular permeability due to induced VEGF expression. It is thought to be a consequence of an adaptive or evasive tumour response [40]. |
Sorafenib | Sorafenib inhibits VEGFR. Mangiameli et al. proved that after sorafenib therapy there is an inhibition of tumour growth and metastasis [223]. In patients with metastatic cutaneous melanoma, sorafenib monotherapy has not shown significant antitumour activity [224]. Filali et al. compared the treatment of patients with metastatic melanoma (not including uvea) with carboplatin, paclitaxel and sorafenib or placebo, where the results of the phase 3 study showed no relevance to overall survival [40]. |
Sunitinib | Sunitinib also inhibits VEGFR [225]. A preclinical phase 2 study demonstrated the benefit of sunitinib monotherapy in patients with advanced metastatic melanoma [40]. |
Product | Type | Target | Status | Ref. |
---|---|---|---|---|
Bevacizumab sold as Avastin® | Monoclonal antibody Angiogenesis inhibitor | VEGF | Authorized for the treatment of various tumour types in EU and USA | [231,232,233] |
Ipilimumab sold as Yervoy® | Monoclonal antibody Immune system modulator | CTLA-4 | Authorized for melanoma and carcinoma treatment in EU and USA | [234,235,236] |
Ranibizumab sold as Lucentis® | Monoclonal antibody fragment Angiogenesis inhibitor | VEGF-A | Authorized for macular edema and diabetic retinopathy treatment in EU and USA | [237,238,239] |
Pembrolizumab sold as Keytruda® | Monoclonal antibody Immune system modulator | PD-1 | Authorized for the treatment of melanoma and other tumour types in EU and USA | [41,240,241] |
Sunitinib sold as Keytruda® | Multiple receptor tyrosine kinases inhibitor Angiogenesis inhibitor | c-KIT VEGFR PDGFR M-CSFR | Authorized for the treatment of various tumour types in EU and USA | [242,243,244] |
Sorafenib sold as Nexavar® | Synthetic drug Multikinase inhibitor Angiogenesis inhibitor | Protein kinase | Authorized for the treatment of various carcinoma types in EU and USA | [245,246,247,248] |
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Souto, E.B.; Campos, J.R.; Da Ana, R.; Fangueiro, J.F.; Martins-Gomes, C.; Durazzo, A.; Lucarini, M.; Sánchez López, E.; Espina, M.; García, M.L.; et al. Diabetic Retinopathy and Ocular Melanoma: How Far We Are? Appl. Sci. 2020, 10, 2777. https://doi.org/10.3390/app10082777
Souto EB, Campos JR, Da Ana R, Fangueiro JF, Martins-Gomes C, Durazzo A, Lucarini M, Sánchez López E, Espina M, García ML, et al. Diabetic Retinopathy and Ocular Melanoma: How Far We Are? Applied Sciences. 2020; 10(8):2777. https://doi.org/10.3390/app10082777
Chicago/Turabian StyleSouto, Eliana B., Joana R. Campos, Raquel Da Ana, Joana F. Fangueiro, Carlos Martins-Gomes, Alessandra Durazzo, Massimo Lucarini, Elena Sánchez López, Marta Espina, Maria Luisa García, and et al. 2020. "Diabetic Retinopathy and Ocular Melanoma: How Far We Are?" Applied Sciences 10, no. 8: 2777. https://doi.org/10.3390/app10082777