Targeting STAT3 and STAT5 in Cancer
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...
שמור ב:
| פורמט: | Online |
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| שפה: | אנגלית |
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MDPI - Multidisciplinary Digital Publishing Institute
2021
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| נושאים: | |
| גישה מקוונת: | ONIX_20210501_9783039430369_821 |
| תגים: |
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| _version_ | 1869520420057645056 |
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| collection | Directory of Open Access Books |
| description | 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. |
| format | Online |
| id | doab-20.500.12854ir-69075 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI - Multidisciplinary Digital Publishing Institute |
| publisherStr | MDPI - Multidisciplinary Digital Publishing Institute |
| record_format | ojs |
| spelling | doab-20.500.12854ir-690752024-03-28T03:33:31Z Targeting STAT3 and STAT5 in Cancer Moriggl, Richard Gunning, Patrick Keserü, György Miklós 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 n/a thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general thema EDItEUR::P Mathematics and Science::PS Biology, life sciences 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. 2021-05-01T15:40:34Z 2021-05-01T15:40:34Z 2020 book ONIX_20210501_9783039430369_821 9783039430369 9783039430376 https://directory.doabooks.org/handle/20.500.12854/69075 eng application/octet-stream Attribution 4.0 International https://mdpi.com/books/pdfview/book/2844 https://mdpi.com/books/pdfview/book/2844 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-03943-037-6 10.3390/books978-3-03943-037-6 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783039430369 9783039430376 578 Basel, Switzerland open access |
| spellingShingle | 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 n/a thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general thema EDItEUR::P Mathematics and Science::PS Biology, life sciences Targeting STAT3 and STAT5 in Cancer |
| title | Targeting STAT3 and STAT5 in Cancer |
| title_full | Targeting STAT3 and STAT5 in Cancer |
| title_fullStr | Targeting STAT3 and STAT5 in Cancer |
| title_full_unstemmed | Targeting STAT3 and STAT5 in Cancer |
| title_short | Targeting STAT3 and STAT5 in Cancer |
| title_sort | targeting stat3 and stat5 in cancer |
| topic | 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 n/a thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| topic_facet | 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 n/a thema EDItEUR::G Reference, Information and Interdisciplinary subjects::GP Research and information: general thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| url | ONIX_20210501_9783039430369_821 |