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Every minute, 34 new patients are diagnosed with cancer globally. Although over the past 50 years treatments have improved and survival rates have increased dramatically for several types of cancers, many remain incurable. Several aggressive types of blood and solid cancers form when mutations occur in a critical cellular signaling pathway, the JAK-STAT pathway; (Janus Kinase-Signal Transducer and Activator of Transcription). Currently, there are no clinically available drugs that target the oncogenic STAT3/5 proteins in particular or their Gain of Function hyperactive mutant products. Here, we summarize targeting approaches on STAT3/5, as the field moves towards clinical applications as well as we illuminate on upstream or downstream JAK-STAT pathway interference with kinase inhibitors, heat shock protein blockers or changing nuclear import/export processes. We cover the design paradigms and medicinal chemistry approaches to illuminate progress and challenges in understanding the pleiotropic role of STAT3 and STAT5 in oncogenesis, the microenvironment, the immune system in particular, all culminating in a complex interplay towards cancer progression.

Research & information: general --- Biology, life sciences --- multiple myeloma --- STAT3 --- S3I-1757 --- nanoparticle --- CD38 --- siRNA/RNAi --- polyethylenimine --- PEI --- lipopolyplex --- siRNA delivery --- glioma --- glioblastoma --- STAT5 --- AKT --- ERK1/2 --- prolactin --- androgens --- prostate cancer --- knockout --- escape mechanisms --- stem/progenitor cells --- cell hierarchy --- cancer --- CD4+ T cells --- CD8+ T cells --- myeloid cells --- immune check point --- hepatitis C virus (HCV) --- cirrhosis --- hepatocellular carcinoma (HCC) --- endoplasmic reticulum (ER) stress --- oxidative stress (OS) --- unfolded protein response (UPR) --- microRNA-122 (miR-122) --- nuclear factor erythroid 2-related factor 2 (NRF2) --- signal transducer and activator of transcription 3 (STAT3) --- hepatocyte nuclear factor 4 alpha (HNF4A) --- solid cancers --- cell cycle --- apoptosis --- inflammation --- mitochondria --- stemness --- tumor suppression --- melanoma --- autoimmune disease --- immunotherapy --- tumor-immune cell interactions --- breast cancer --- PD-L1 --- M2 macrophages --- NK cells --- STAT3 inhibitor XIII --- hedging --- transaction costs --- dynamic programming --- risk management --- post-decision state variable --- cancer progression --- cancer-stem cell --- cytokine --- therapy resistance --- metastasis --- immunosuppression --- tumor microenvironment --- proliferation --- tyrosine kinase 2 --- JAK family of protein tyrosine kinases --- signal transducer and activator of transcription --- cytokine receptor signaling --- gain-of-function mutation --- tumorigenesis --- ADAM17 --- interleukin-6 --- trans-signaling --- epidermal growth factor receptor (EGF-R) --- shedding --- metalloprotease --- tumor necrosis factor alpha (TNFα) --- inflammation associated cancer --- colon cancer --- lung cancer --- SH2 domain --- mutations --- autosomal-dominant hyper IgE syndrome --- inflammatory hepatocellular adenomas --- T-cell large granular lymphocytic leukemia --- T-cell prolymphocytic leukemia --- growth hormone insensitivity syndrome --- nuclear pore complex --- nuclear transport receptors --- nucleocytoplasmic shuttling --- targeting --- tumor-associated macrophages --- adoptive T cell therapy --- immune suppression --- STAT transcription factors --- JAK --- STAT --- T-PLL --- T-cell leukemia --- meta-analysis --- STAT5B signaling --- small-molecule inhibitors --- cancer models --- companion animals --- comparative oncology --- pharmacological inhibitor --- STAT5 signaling --- chemotherapy resistance --- myeloid leukemia --- heat shock proteins --- chaperones --- stabilization --- targeted therapy --- ovarian cancer --- hematopoietic cancers --- therapeutic targeting --- pharmacological inhibitors --- mTOR --- Bone Marrow Failure Syndromes --- lymphocytes --- lymphoma --- T-cells --- RHOA --- NGS --- MPN --- JAK2 V617F --- neoplastic stem cells --- multiple myeloma --- STAT3 --- S3I-1757 --- nanoparticle --- CD38 --- siRNA/RNAi --- polyethylenimine --- PEI --- lipopolyplex --- siRNA delivery --- glioma --- glioblastoma --- STAT5 --- AKT --- ERK1/2 --- prolactin --- androgens --- prostate cancer --- knockout --- escape mechanisms --- stem/progenitor cells --- cell hierarchy --- cancer --- CD4+ T cells --- CD8+ T cells --- myeloid cells --- immune check point --- hepatitis C virus (HCV) --- cirrhosis --- hepatocellular carcinoma (HCC) --- endoplasmic reticulum (ER) stress --- oxidative stress (OS) --- unfolded protein response (UPR) --- microRNA-122 (miR-122) --- nuclear factor erythroid 2-related factor 2 (NRF2) --- signal transducer and activator of transcription 3 (STAT3) --- hepatocyte nuclear factor 4 alpha (HNF4A) --- solid cancers --- cell cycle --- apoptosis --- inflammation --- mitochondria --- stemness --- tumor suppression --- melanoma --- autoimmune disease --- immunotherapy --- tumor-immune cell interactions --- breast cancer --- PD-L1 --- M2 macrophages --- NK cells --- STAT3 inhibitor XIII --- hedging --- transaction costs --- dynamic programming --- risk management --- post-decision state variable --- cancer progression --- cancer-stem cell --- cytokine --- therapy resistance --- metastasis --- immunosuppression --- tumor microenvironment --- proliferation --- tyrosine kinase 2 --- JAK family of protein tyrosine kinases --- signal transducer and activator of transcription --- cytokine receptor signaling --- gain-of-function mutation --- tumorigenesis --- ADAM17 --- interleukin-6 --- trans-signaling --- epidermal growth factor receptor (EGF-R) --- shedding --- metalloprotease --- tumor necrosis factor alpha (TNFα) --- inflammation associated cancer --- colon cancer --- lung cancer --- SH2 domain --- mutations --- autosomal-dominant hyper IgE syndrome --- inflammatory hepatocellular adenomas --- T-cell large granular lymphocytic leukemia --- T-cell prolymphocytic leukemia --- growth hormone insensitivity syndrome --- nuclear pore complex --- nuclear transport receptors --- nucleocytoplasmic shuttling --- targeting --- tumor-associated macrophages --- adoptive T cell therapy --- immune suppression --- STAT transcription factors --- JAK --- STAT --- T-PLL --- T-cell leukemia --- meta-analysis --- STAT5B signaling --- small-molecule inhibitors --- cancer models --- companion animals --- comparative oncology --- pharmacological inhibitor --- STAT5 signaling --- chemotherapy resistance --- myeloid leukemia --- heat shock proteins --- chaperones --- stabilization --- targeted therapy --- ovarian cancer --- hematopoietic cancers --- therapeutic targeting --- pharmacological inhibitors --- mTOR --- Bone Marrow Failure Syndromes --- lymphocytes --- lymphoma --- T-cells --- RHOA --- NGS --- MPN --- JAK2 V617F --- neoplastic stem cells

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Vision is the most important sense in higher mammals. The retina is the first step in visual processing and the window to the brain. It is not surprising that problems arising in the retina lead to moderate to severe visual impairments. We offer here a collection of reviews as well as original papers dealing with various aspects of retinal function as well as dysfunction. New approaches in retinal research are described, such as the expression and localization of the endocannabinoid system in the normal retina and the role of cannabinoid receptors that could offer new avenues of research in the development of potential treatments for retinal diseases. Moreover, new insights are offered in advancing knowledge towards the prevention and cure of visual pathologies, mainly AMD, RP, and diabetic retinopathy.

Medicine --- Neurosciences --- eye --- retina --- development --- vascularization --- hypoxia --- autophagy --- programmed cell death --- cellular senescence --- retinogenesis --- altricial bird species --- precocial bird species --- senescence-associated galactosidase activity --- diabetes mellitus --- retinopathy --- microvascular --- complication --- optical coherence tomography --- angiography --- black --- African-American --- systemic disease --- biomarker --- retinal degenerative diseases --- mesenchymal stem cells --- stem cell therapy --- experimental models --- clinical trials --- AMD --- age-related macular degeneration --- trichostatin A (TSA) --- HDAC --- histone deacetylase --- vascular endothelial growth factor (VEGF) --- retinal degeneration --- endoplasmic reticulum --- stress response --- unfolded protein response --- GRP78 --- retinal glial cell --- diabetic retinopathy --- zebrafish --- neurovascular unit --- microvascular complications and dysfunction --- metabolism --- motor protein --- myosin 1C --- photoreceptor --- rhodopsin --- outer segments --- visual function --- macroglia --- astrocytes --- Müller cells --- optic nerve crush --- retinal ganglion cells --- spinal cord injury --- signal transducer and activator of transcription 3 --- epidermal growth factor --- Drp1 --- apoptosis --- mitochondria --- microglia --- neurodegeneration --- multiple sclerosis --- retinal microglia --- microglia morphotype --- light damage --- functional analysis --- early detection --- remodeling --- lactate --- GPR81 --- HCAR1 --- growth cone --- dLGN --- axon --- 3,5-DHBA --- kallikrein-kinin system --- kinin receptors --- GFAP --- osteopontin --- retinal detachment --- diabetes --- antioxidants --- bioenergetics --- respiration --- ATP --- glucagon-like peptide-1 --- exendin-4 --- catalase --- immunohistochemistry --- electron microscopy --- Charles Bonnet syndrome --- EEG --- visual hallucination --- resting state --- high-fat diet --- gut microbiome --- gut-retina axis --- RNA sequencing --- germ-free mice --- complement cascade --- angiogenesis --- retinal inflammation --- AII amacrine cell --- Prox1 --- parvalbumin --- gap junction --- eccentricity --- ON/OFF asymmetry --- arterioles --- betulinic acid --- ischemia-reperfusion injury --- reactive oxygen species --- retinal vessels --- retinal fluorescence imaging --- amyloid --- cognitive decline --- Alzheimer's disease --- optic neuritis --- oxidative stress --- neuroprotection --- fingolimod --- iPSC-RPE --- retinal pigment epithelium --- immunodeficient RCS rat --- ultrathin parylene --- retinal transplantation --- CD4+CD25+ --- inflammation --- iPSC --- typical cannabinoid receptors --- atypical cannabinoid receptors --- electroretinography --- monkeys --- visual system --- eye inflammation --- lipopolysaccharide --- natural bioactive extracts --- Ac2-26 --- FPR receptor --- inflammatory mediators --- retinal light injury --- LED screen --- optical filter --- retinal protection --- regeneration --- progenitor cell --- hyperglycemia --- photoreceptors --- neurod --- Notch --- eye --- retina --- development --- vascularization --- hypoxia --- autophagy --- programmed cell death --- cellular senescence --- retinogenesis --- altricial bird species --- precocial bird species --- senescence-associated galactosidase activity --- diabetes mellitus --- retinopathy --- microvascular --- complication --- optical coherence tomography --- angiography --- black --- African-American --- systemic disease --- biomarker --- retinal degenerative diseases --- mesenchymal stem cells --- stem cell therapy --- experimental models --- clinical trials --- AMD --- age-related macular degeneration --- trichostatin A (TSA) --- HDAC --- histone deacetylase --- vascular endothelial growth factor (VEGF) --- retinal degeneration --- endoplasmic reticulum --- stress response --- unfolded protein response --- GRP78 --- retinal glial cell --- diabetic retinopathy --- zebrafish --- neurovascular unit --- microvascular complications and dysfunction --- metabolism --- motor protein --- myosin 1C --- photoreceptor --- rhodopsin --- outer segments --- visual function --- macroglia --- astrocytes --- Müller cells --- optic nerve crush --- retinal ganglion cells --- spinal cord injury --- signal transducer and activator of transcription 3 --- epidermal growth factor --- Drp1 --- apoptosis --- mitochondria --- microglia --- neurodegeneration --- multiple sclerosis --- retinal microglia --- microglia morphotype --- light damage --- functional analysis --- early detection --- remodeling --- lactate --- GPR81 --- HCAR1 --- growth cone --- dLGN --- axon --- 3,5-DHBA --- kallikrein-kinin system --- kinin receptors --- GFAP --- osteopontin --- retinal detachment --- diabetes --- antioxidants --- bioenergetics --- respiration --- ATP --- glucagon-like peptide-1 --- exendin-4 --- catalase --- immunohistochemistry --- electron microscopy --- Charles Bonnet syndrome --- EEG --- visual hallucination --- resting state --- high-fat diet --- gut microbiome --- gut-retina axis --- RNA sequencing --- germ-free mice --- complement cascade --- angiogenesis --- retinal inflammation --- AII amacrine cell --- Prox1 --- parvalbumin --- gap junction --- eccentricity --- ON/OFF asymmetry --- arterioles --- betulinic acid --- ischemia-reperfusion injury --- reactive oxygen species --- retinal vessels --- retinal fluorescence imaging --- amyloid --- cognitive decline --- Alzheimer's disease --- optic neuritis --- oxidative stress --- neuroprotection --- fingolimod --- iPSC-RPE --- retinal pigment epithelium --- immunodeficient RCS rat --- ultrathin parylene --- retinal transplantation --- CD4+CD25+ --- inflammation --- iPSC --- typical cannabinoid receptors --- atypical cannabinoid receptors --- electroretinography --- monkeys --- visual system --- eye inflammation --- lipopolysaccharide --- natural bioactive extracts --- Ac2-26 --- FPR receptor --- inflammatory mediators --- retinal light injury --- LED screen --- optical filter --- retinal protection --- regeneration --- progenitor cell --- hyperglycemia --- photoreceptors --- neurod --- Notch

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• Reference Manager
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Vision is the most important sense in higher mammals. The retina is the first step in visual processing and the window to the brain. It is not surprising that problems arising in the retina lead to moderate to severe visual impairments. We offer here a collection of reviews as well as original papers dealing with various aspects of retinal function as well as dysfunction. New approaches in retinal research are described, such as the expression and localization of the endocannabinoid system in the normal retina and the role of cannabinoid receptors that could offer new avenues of research in the development of potential treatments for retinal diseases. Moreover, new insights are offered in advancing knowledge towards the prevention and cure of visual pathologies, mainly AMD, RP, and diabetic retinopathy.

eye --- retina --- development --- vascularization --- hypoxia --- autophagy --- programmed cell death --- cellular senescence --- retinogenesis --- altricial bird species --- precocial bird species --- senescence-associated galactosidase activity --- diabetes mellitus --- retinopathy --- microvascular --- complication --- optical coherence tomography --- angiography --- black --- African-American --- systemic disease --- biomarker --- retinal degenerative diseases --- mesenchymal stem cells --- stem cell therapy --- experimental models --- clinical trials --- AMD --- age-related macular degeneration --- trichostatin A (TSA) --- HDAC --- histone deacetylase --- vascular endothelial growth factor (VEGF) --- retinal degeneration --- endoplasmic reticulum --- stress response --- unfolded protein response --- GRP78 --- retinal glial cell --- diabetic retinopathy --- zebrafish --- neurovascular unit --- microvascular complications and dysfunction --- metabolism --- motor protein --- myosin 1C --- photoreceptor --- rhodopsin --- outer segments --- visual function --- macroglia --- astrocytes --- Müller cells --- optic nerve crush --- retinal ganglion cells --- spinal cord injury --- signal transducer and activator of transcription 3 --- epidermal growth factor --- Drp1 --- apoptosis --- mitochondria --- microglia --- neurodegeneration --- multiple sclerosis --- retinal microglia --- microglia morphotype --- light damage --- functional analysis --- early detection --- remodeling --- lactate --- GPR81 --- HCAR1 --- growth cone --- dLGN --- axon --- 3,5-DHBA --- kallikrein-kinin system --- kinin receptors --- GFAP --- osteopontin --- retinal detachment --- diabetes --- antioxidants --- bioenergetics --- respiration --- ATP --- glucagon-like peptide-1 --- exendin-4 --- catalase --- immunohistochemistry --- electron microscopy --- Charles Bonnet syndrome --- EEG --- visual hallucination --- resting state --- high-fat diet --- gut microbiome --- gut-retina axis --- RNA sequencing --- germ-free mice --- complement cascade --- angiogenesis --- retinal inflammation --- AII amacrine cell --- Prox1 --- parvalbumin --- gap junction --- eccentricity --- ON/OFF asymmetry --- arterioles --- betulinic acid --- ischemia-reperfusion injury --- reactive oxygen species --- retinal vessels --- retinal fluorescence imaging --- amyloid --- cognitive decline --- Alzheimer’s disease --- optic neuritis --- oxidative stress --- neuroprotection --- fingolimod --- iPSC-RPE --- retinal pigment epithelium --- immunodeficient RCS rat --- ultrathin parylene --- retinal transplantation --- CD4+CD25+ --- inflammation --- iPSC --- typical cannabinoid receptors --- atypical cannabinoid receptors --- electroretinography --- monkeys --- visual system --- eye inflammation --- lipopolysaccharide --- natural bioactive extracts --- Ac2-26 --- FPR receptor --- inflammatory mediators --- retinal light injury --- LED screen --- optical filter --- retinal protection --- regeneration --- progenitor cell --- hyperglycemia --- photoreceptors --- neurod --- Notch --- n/a --- Müller cells --- Alzheimer's disease