Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation

Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), w...

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Published in	Cancers Vol. 16; no. 7; p. 1387
Main Authors	Wang, Weiyuan, Lopez McDonald, Melanie Cristina, Hariprasad, Rajashree, Hamilton, Tiara, Frank, David A.
Format	Journal Article
Language	English
Published	Switzerland MDPI AG 01.04.2024
Subjects	Angiogenesis Antimitotic agents Antineoplastic agents Apoptosis B cells Cancer Cancer therapies Care and treatment Cytokines Cytoplasm Development and progression DNA binding proteins Gene expression Genes Genetic aspects Growth factors Health aspects Immune system Immunosuppressive agents Kinases Leukemia Localization Metastasis Mutation Phosphorylation Physiological aspects Proteins Stat protein Stat3 protein Stat5 protein Transcription activation Transcription factors Tumorigenesis cancer therapy STAT5 cancer immunity STAT3
Online Access	Get full text
ISSN	2072-6694 2072-6694
DOI	10.3390/cancers16071387

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Abstract	Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.
AbstractList	Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics. Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics. Cancer is the second leading cause of death worldwide, accounting for nearly one in six deaths. One of the key underlying factors distinguishing a cancer cell from a normal cell is the pattern of expression of genes. Proteins that regulate gene expression, called transcription factors, are abnormally regulated in cancer cells, particularly a group of proteins called STATs. This causes cancer cells to survive, proliferate excessively, and escape killing by the immune system. Since normal cells can survive adequately without full STAT function, targeting these proteins is an attractive approach for a new generation of more effective and less toxic cancer therapies. In this review, we summarize the current knowledge of STAT function in cancer and the advances and challenges in developing drugs to target them. Simple SummaryCancer is the second leading cause of death worldwide, accounting for nearly one in six deaths. One of the key underlying factors distinguishing a cancer cell from a normal cell is the pattern of expression of genes. Proteins that regulate gene expression, called transcription factors, are abnormally regulated in cancer cells, particularly a group of proteins called STATs. This causes cancer cells to survive, proliferate excessively, and escape killing by the immune system. Since normal cells can survive adequately without full STAT function, targeting these proteins is an attractive approach for a new generation of more effective and less toxic cancer therapies. In this review, we summarize the current knowledge of STAT function in cancer and the advances and challenges in developing drugs to target them.AbstractDespite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics. Cancer is the second leading cause of death worldwide, accounting for nearly one in six deaths. One of the key underlying factors distinguishing a cancer cell from a normal cell is the pattern of expression of genes. Proteins that regulate gene expression, called transcription factors, are abnormally regulated in cancer cells, particularly a group of proteins called STATs. This causes cancer cells to survive, proliferate excessively, and escape killing by the immune system. Since normal cells can survive adequately without full STAT function, targeting these proteins is an attractive approach for a new generation of more effective and less toxic cancer therapies. In this review, we summarize the current knowledge of STAT function in cancer and the advances and challenges in developing drugs to target them. Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is driven by the inappropriate activation of transcription factors. In particular, signal transducers and activators of transcription (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, and differentiation, are frequently activated inappropriately in a wide spectrum of human cancers. Multiple signaling pathways converge on the STATs, highlighting their importance in the development and progression of oncogenic diseases. STAT3 and STAT5 are two members of the STAT protein family that are the most frequently activated in cancers and can drive cancer pathogenesis directly. The development of inhibitors targeting STAT3 and STAT5 has been the subject of intense investigations in the last decade, although effective treatment options remain limited. In this review, we investigate the specific roles of STAT3 and STAT5 in normal physiology and cancer biology, discuss the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators, and offer insights into novel therapeutic strategies to identify STAT inhibitors as cancer therapeutics.
Audience	Academic
Author	Frank, David A. Wang, Weiyuan Lopez McDonald, Melanie Cristina Hariprasad, Rajashree Hamilton, Tiara
Author_xml	– sequence: 1 givenname: Weiyuan surname: Wang fullname: Wang, Weiyuan – sequence: 2 givenname: Melanie Cristina surname: Lopez McDonald fullname: Lopez McDonald, Melanie Cristina – sequence: 3 givenname: Rajashree surname: Hariprasad fullname: Hariprasad, Rajashree – sequence: 4 givenname: Tiara surname: Hamilton fullname: Hamilton, Tiara – sequence: 5 givenname: David A. orcidid: 0000-0002-7698-8364 surname: Frank fullname: Frank, David A.
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CitedBy_id	crossref_primary_10_1016_j_jhepr_2025_101365 crossref_primary_10_1016_j_neo_2025_101137 crossref_primary_10_3389_fimmu_2024_1388176 crossref_primary_10_1158_1078_0432_CCR_24_1692
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Snippet	Despite advances in our understanding of molecular aspects of oncogenesis, cancer remains a leading cause of death. The malignant behavior of a cancer cell is... Cancer is the second leading cause of death worldwide, accounting for nearly one in six deaths. One of the key underlying factors distinguishing a cancer cell... Simple SummaryCancer is the second leading cause of death worldwide, accounting for nearly one in six deaths. One of the key underlying factors distinguishing...
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SubjectTerms	Angiogenesis Antimitotic agents Antineoplastic agents Apoptosis B cells Cancer Cancer therapies Care and treatment Cytokines Cytoplasm Development and progression DNA binding proteins Gene expression Genes Genetic aspects Growth factors Health aspects Immune system Immunosuppressive agents Kinases Leukemia Localization Metastasis Mutation Phosphorylation Physiological aspects Proteins Stat protein Stat3 protein Stat5 protein Transcription activation Transcription factors Tumorigenesis
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Title	Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation
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