Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189211
Yuanyuan Wang, Lei Xue
Esophageal cancer is a significant contributor to cancer-related mortality, and its poor prognosis is primarily attributed to the aggressive nature of the tumor and challenges in early detection. Currently, there are no ideal drugs developed for treatment, making it crucial to explore potential biomarkers and molecular targets for esophageal cancer. FOXP3, as a transcription factor and major regulator of regulatory T cells, not only plays a role in promoting or inhibiting tumor development in various types of cancer cells including esophageal cancer cells but also influences the function of Treg cells by regulating the expression of multiple genes. This paper provides an in-depth discussion on the functional properties, regulatory mechanisms, key signaling pathways, as well as the role and potential application of FOXP3 in treating esophageal cancer. Furthermore, it comprehensively analyzes the complex role of this transcription factor within the tumor immune microenvironment with an aim to aid in developing new potential targets for esophageal cancer treatment.
食管癌是导致癌症相关死亡率的一个重要因素，其预后不良的主要原因是肿瘤的侵袭性和早期检测方面的挑战。目前还没有理想的治疗药物，因此探索食管癌的潜在生物标志物和分子靶点至关重要。FOXP3 作为转录因子和调节性 T 细胞的主要调控因子，不仅在促进或抑制包括食管癌细胞在内的各类癌细胞的肿瘤发生发展中发挥作用，还通过调控多种基因的表达影响 Treg 细胞的功能。本文深入探讨了 FOXP3 的功能特性、调控机制、关键信号通路以及在食管癌治疗中的作用和潜在应用。此外，它还全面分析了该转录因子在肿瘤免疫微环境中的复杂作用，旨在帮助开发食管癌治疗的新潜在靶点。
{"title":"Decoding the role of FOXP3 in esophageal cancer: Underlying mechanisms and therapeutic implications","authors":"Yuanyuan Wang, Lei Xue","doi":"10.1016/j.bbcan.2024.189211","DOIUrl":"10.1016/j.bbcan.2024.189211","url":null,"abstract":"<div><div>Esophageal cancer is a significant contributor to cancer-related mortality, and its poor prognosis is primarily attributed to the aggressive nature of the tumor and challenges in early detection. Currently, there are no ideal drugs developed for treatment, making it crucial to explore potential biomarkers and molecular targets for esophageal cancer. FOXP3, as a transcription factor and major regulator of regulatory T cells, not only plays a role in promoting or inhibiting tumor development in various types of cancer cells including esophageal cancer cells but also influences the function of Treg cells by regulating the expression of multiple genes. This paper provides an in-depth discussion on the functional properties, regulatory mechanisms, key signaling pathways, as well as the role and potential application of FOXP3 in treating esophageal cancer. Furthermore, it comprehensively analyzes the complex role of this transcription factor within the tumor immune microenvironment with an aim to aid in developing new potential targets for esophageal cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189211"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189207
Dandan Shi , Jiejing Tao , Shuli Man , Ning Zhang , Long Ma , Lanping Guo , Luqi Huang , Wenyuan Gao
Cancer remains one of the most difficult human diseases to overcome because of its complexity and diversity. Signal transducers and transcriptional activators 3 (STAT3) protein has been found to be overexpressed in a wide range of cancer types. Hyperactivation of STAT3 is particularly associated with low survival in cancer patients. This review summarizes the specific molecular mechanisms of STAT3 in cancer development. STAT3 is activated by extracellular signals in the cytoplasm, interacts with different enzymes in the nucleus, mitochondria or endoplasmic reticulum, and subsequently participates in cancer development. The phosphorylated STAT3 at tyrosine 705 site (YP-STAT3) enters the nucleus and regulates a number of tumor-related biological processes such as angiogenesis, migration invasion, cell proliferation and cancer cell stemness. In contrast, the phosphorylated STAT3 at serine 727 site (SP-STAT3) is found on the mitochondria, affects electron respiration transport chain activity and thereby prevents tumor cell apoptosis. SP-STAT3 also appears on the mitochondria-associated endoplasmic reticulum membrane, influences the flow of Ca2+, and affects tumor progression. In addition, we summarize the direct and indirect inhibitors of STAT3 which are currently undergoing clinical studies. Some of them such as TTI101 and BBI608 have been approved by the FDA for the treatment of certain cancers. All in all, STAT3 plays an important role in cancer progression and becomes a potential target for cancer treatment.
{"title":"Structure, function, signaling pathways and clinical therapeutics: The translational potential of STAT3 as a target for cancer therapy","authors":"Dandan Shi , Jiejing Tao , Shuli Man , Ning Zhang , Long Ma , Lanping Guo , Luqi Huang , Wenyuan Gao","doi":"10.1016/j.bbcan.2024.189207","DOIUrl":"10.1016/j.bbcan.2024.189207","url":null,"abstract":"<div><div>Cancer remains one of the most difficult human diseases to overcome because of its complexity and diversity. Signal transducers and transcriptional activators 3 (STAT3) protein has been found to be overexpressed in a wide range of cancer types. Hyperactivation of STAT3 is particularly associated with low survival in cancer patients. This review summarizes the specific molecular mechanisms of STAT3 in cancer development. STAT3 is activated by extracellular signals in the cytoplasm, interacts with different enzymes in the nucleus, mitochondria or endoplasmic reticulum, and subsequently participates in cancer development. The phosphorylated STAT3 at tyrosine 705 site (YP-STAT3) enters the nucleus and regulates a number of tumor-related biological processes such as angiogenesis, migration invasion, cell proliferation and cancer cell stemness. In contrast, the phosphorylated STAT3 at serine 727 site (SP-STAT3) is found on the mitochondria, affects electron respiration transport chain activity and thereby prevents tumor cell apoptosis. SP-STAT3 also appears on the mitochondria-associated endoplasmic reticulum membrane, influences the flow of Ca<sup>2+</sup>, and affects tumor progression. In addition, we summarize the direct and indirect inhibitors of STAT3 which are currently undergoing clinical studies. Some of them such as TTI101 and BBI608 have been approved by the FDA for the treatment of certain cancers. All in all, STAT3 plays an important role in cancer progression and becomes a potential target for cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189207"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189202
Yi-Chieh Yang , Kuo-Hao Ho , Kuo-Tai Hua , Ming-Hsien Chien
The KH-type splicing regulatory protein (KHSRP), also known as KSRP, is an RNA-binding protein that regulates gene expressions through various mechanisms, including messenger (m)RNA degradation, micro (mi)RNA maturation, and transcriptional activity. KSRP has been implicated in a wide range of physiological and pathological processes, with emerging evidence highlighting its role in modulating diverse aspects of cancer behaviors. In this review, we provide a comprehensive overview of KSRP's clinical relevance and its multifaceted regulatory mechanisms in cancer. Our extensive pan-cancer analysis uncovers associations of KSRP with clinical outcomes and identifies cell cycle progression as a key signaling pathway correlated with KSRP expression. Furthermore, we identify miR-17-5p as critical miRNAs positively correlated with KSRP, and it is associated with poor survival in various cancers. Collectively, this review offers new insights into the potential of KSRP as a target for therapeutic strategies in cancer treatment.
{"title":"Roles of K(H)SRP in modulating gene transcription throughout cancer progression: Insights from cellular studies to clinical perspectives","authors":"Yi-Chieh Yang , Kuo-Hao Ho , Kuo-Tai Hua , Ming-Hsien Chien","doi":"10.1016/j.bbcan.2024.189202","DOIUrl":"10.1016/j.bbcan.2024.189202","url":null,"abstract":"<div><div>The KH-type splicing regulatory protein (KHSRP), also known as KSRP, is an RNA-binding protein that regulates gene expressions through various mechanisms, including messenger (m)RNA degradation, micro (mi)RNA maturation, and transcriptional activity. KSRP has been implicated in a wide range of physiological and pathological processes, with emerging evidence highlighting its role in modulating diverse aspects of cancer behaviors. In this review, we provide a comprehensive overview of KSRP's clinical relevance and its multifaceted regulatory mechanisms in cancer. Our extensive pan-cancer analysis uncovers associations of KSRP with clinical outcomes and identifies cell cycle progression as a key signaling pathway correlated with KSRP expression. Furthermore, we identify miR-17-5p as critical miRNAs positively correlated with KSRP, and it is associated with poor survival in various cancers. Collectively, this review offers new insights into the potential of KSRP as a target for therapeutic strategies in cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189202"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cytokines are the crucial signaling proteins that mediate the crosstalks between the cells of tumor microenvironment (TME). Interferon-1 (IFN-1) are the important cytokines that are widely known for their tumor suppressive roles comprising of cancer cell intrinsic and extrinsic mechanisms. Despite having known antitumor effects, IFN-1 are also reported to have tumor promoting functions under varying circumstances. This dichotomy in the functions of IFN-1 is largely attributed to the acute and chronic activation of IFN-1 signaling in TME. The chronic activation of IFN-1 signaling in tumor cells results in altered stimulation of downstream pathways that result in the expression of tumor promoting proteins, while the acute IFN-1 signaling activation maintains its tumor inhibiting functions. In the present review, we have discussed the anti- and pro-tumor actions of IFN-1 signaling under acute and chronic IFN-1 signaling activation. We have also discussed the downstream changes in signaling components that result in tumor supportive functions of a constitutive IFN-1 signaling. We have further discussed the possible strategies to overcome the detrimental effects of chronic IFN-1 pathway activation and to successfully employ IFN-1 for their beneficial anti-tumor effects.
{"title":"The curious case of type I interferon signaling in cancer","authors":"Abu Sufiyan Chhipa , Valentina Boscaro , Margherita Gallicchio , Snehal Patel","doi":"10.1016/j.bbcan.2024.189204","DOIUrl":"10.1016/j.bbcan.2024.189204","url":null,"abstract":"<div><div>Cytokines are the crucial signaling proteins that mediate the crosstalks between the cells of tumor microenvironment (TME). Interferon-1 (IFN-1) are the important cytokines that are widely known for their tumor suppressive roles comprising of cancer cell intrinsic and extrinsic mechanisms. Despite having known antitumor effects, IFN-1 are also reported to have tumor promoting functions under varying circumstances. This dichotomy in the functions of IFN-1 is largely attributed to the acute and chronic activation of IFN-1 signaling in TME. The chronic activation of IFN-1 signaling in tumor cells results in altered stimulation of downstream pathways that result in the expression of tumor promoting proteins, while the acute IFN-1 signaling activation maintains its tumor inhibiting functions. In the present review, we have discussed the anti- and pro-tumor actions of IFN-1 signaling under acute and chronic IFN-1 signaling activation. We have also discussed the downstream changes in signaling components that result in tumor supportive functions of a constitutive IFN-1 signaling. We have further discussed the possible strategies to overcome the detrimental effects of chronic IFN-1 pathway activation and to successfully employ IFN-1 for their beneficial anti-tumor effects.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189204"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189210
Qi Wang , Bairen Pang , Joseph Bucci , Junhui Jiang , Yong Li
Current approaches for prostate cancer (PCa) diagnosis and risk stratification require greater accuracy. Extracellular vesicles and particles (EVPs) containing diverse cargos from parent cells are released into the extracellular microenvironment and play a critical role in intercellular communication. Accumulating evidence demonstrates that EVPs are emerging as a promising focus for the exploration of cancer biomarkers and therapeutic targets. However, the precise categorisation and nomenclature of EVP subpopulations remains challenging due to their compositional complexity, inherent heterogeneity in molecular composition, and structure. The recent identification of two novel non-vesicular extracellular particle subtypes, exomeres and supermeres, has altered our understanding of the distinct subpopulations of EVPs and their roles in biological and physiological processes. Here, we discuss recent advances in the field of EVPs, describe characteristics of EVP subpopulations, focus on the application and potential of EVPs in PCa diagnosis and risk stratification by liquid biopsy, and highlight the major challenges and prospects of EVP research in PCa area.
{"title":"The emerging role of extracellular vesicles and particles in prostate cancer diagnosis, and risk stratification","authors":"Qi Wang , Bairen Pang , Joseph Bucci , Junhui Jiang , Yong Li","doi":"10.1016/j.bbcan.2024.189210","DOIUrl":"10.1016/j.bbcan.2024.189210","url":null,"abstract":"<div><div>Current approaches for prostate cancer (PCa) diagnosis and risk stratification require greater accuracy. Extracellular vesicles and particles (EVPs) containing diverse cargos from parent cells are released into the extracellular microenvironment and play a critical role in intercellular communication. Accumulating evidence demonstrates that EVPs are emerging as a promising focus for the exploration of cancer biomarkers and therapeutic targets. However, the precise categorisation and nomenclature of EVP subpopulations remains challenging due to their compositional complexity, inherent heterogeneity in molecular composition, and structure. The recent identification of two novel non-vesicular extracellular particle subtypes, exomeres and supermeres, has altered our understanding of the distinct subpopulations of EVPs and their roles in biological and physiological processes. Here, we discuss recent advances in the field of EVPs, describe characteristics of EVP subpopulations, focus on the application and potential of EVPs in PCa diagnosis and risk stratification by liquid biopsy, and highlight the major challenges and prospects of EVP research in PCa area.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189210"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189205
Sameer Kumar Panda , Nirmal Robinson , Vincenzo Desiderio
Drug resistance caused by the efflux of chemotherapeutic drugs is one of the most challenging obstacles to successful cancer therapy. Several efflux transporters have been identified since the discovery of the P-gp/ABCB1 transporter in 1976. Over the last four decades, researchers have focused on developing efflux transporter inhibitors to overcome drug resistance. However, even with the third-generation inhibitors available, we are still far from effectively inhibiting the efflux transporters. Additionally, Cancer stem cells (CSCs) pose another significant challenge, contributing to cancer recurrence even after successful treatment. The ability of CSCs to enter dormancy and evade detection makes them almost invulnerable to chemotherapeutic drug treatment. In this review, we discuss how Mesenchymal stem cells (MSCs), one of the key components of the Tumor Microenvironment (TME), regulate both the CSCs and efflux transporters. We propose a new approach focusing on MSCs, which can be crucial to successfully address CSCs and efflux transporters.
{"title":"Decoding secret role of mesenchymal stem cells in regulating cancer stem cells and drug resistance","authors":"Sameer Kumar Panda , Nirmal Robinson , Vincenzo Desiderio","doi":"10.1016/j.bbcan.2024.189205","DOIUrl":"10.1016/j.bbcan.2024.189205","url":null,"abstract":"<div><div>Drug resistance caused by the efflux of chemotherapeutic drugs is one of the most challenging obstacles to successful cancer therapy. Several efflux transporters have been identified since the discovery of the P-gp/ABCB1 transporter in 1976. Over the last four decades, researchers have focused on developing efflux transporter inhibitors to overcome drug resistance. However, even with the third-generation inhibitors available, we are still far from effectively inhibiting the efflux transporters. Additionally, Cancer stem cells (CSCs) pose another significant challenge, contributing to cancer recurrence even after successful treatment. The ability of CSCs to enter dormancy and evade detection makes them almost invulnerable to chemotherapeutic drug treatment. In this review, we discuss how Mesenchymal stem cells (MSCs), one of the key components of the Tumor Microenvironment (TME), regulate both the CSCs and efflux transporters. We propose a new approach focusing on MSCs, which can be crucial to successfully address CSCs and efflux transporters.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189205"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189208
Long Li , Zhi-Qiang Ling
Tumor cachexia is a multifactorial syndrome characterized by systemic dysfunction, including anorexia and severe weight loss that is resistant to standard nutritional interventions. It is estimated that approximately 20 % of cancer patients succumb to cachexia in the later stages of their disease. Thus, understanding its pathogenesis is vital for improving therapeutic outcomes. Recent research has focused on the imbalance between energy intake and expenditure in cachexia. Clinically, cachexia presents with anorexia, adipose tissue atrophy, and skeletal muscle wasting, each driven by distinct mechanisms. Anorexia arises primarily from tumor-secreted factors and cancer-induced hormonal disruptions that impair hypothalamic regulation of appetite. Adipose tissue atrophy is largely attributed to enhanced lipolysis, driven by increased activity of enzymes such as adipose triglyceride lipase and hormone-sensitive lipase, coupled with decreased lipoprotein lipase activity. The browning of white adipose tissue, facilitated by uncoupling protein 1, further accelerates fat breakdown by increasing energy expenditure. Skeletal muscle atrophy, a hallmark of cachexia, results from dysregulated protein turnover via the ubiquitin-proteasome and autophagy-lysosomal pathways, as well as mitochondrial dysfunction. Additionally, chemotherapy can exacerbate cachexia. This review examines the molecular mechanisms underlying cancer cachexia and discusses current therapeutic strategies, aiming to inform future research and improve treatment approaches.
{"title":"Mechanisms of cancer cachexia and targeted therapeutic strategies","authors":"Long Li , Zhi-Qiang Ling","doi":"10.1016/j.bbcan.2024.189208","DOIUrl":"10.1016/j.bbcan.2024.189208","url":null,"abstract":"<div><div>Tumor cachexia is a multifactorial syndrome characterized by systemic dysfunction, including anorexia and severe weight loss that is resistant to standard nutritional interventions. It is estimated that approximately 20 % of cancer patients succumb to cachexia in the later stages of their disease. Thus, understanding its pathogenesis is vital for improving therapeutic outcomes. Recent research has focused on the imbalance between energy intake and expenditure in cachexia. Clinically, cachexia presents with anorexia, adipose tissue atrophy, and skeletal muscle wasting, each driven by distinct mechanisms. Anorexia arises primarily from tumor-secreted factors and cancer-induced hormonal disruptions that impair hypothalamic regulation of appetite. Adipose tissue atrophy is largely attributed to enhanced lipolysis, driven by increased activity of enzymes such as adipose triglyceride lipase and hormone-sensitive lipase, coupled with decreased lipoprotein lipase activity. The browning of white adipose tissue, facilitated by uncoupling protein 1, further accelerates fat breakdown by increasing energy expenditure. Skeletal muscle atrophy, a hallmark of cachexia, results from dysregulated protein turnover via the ubiquitin-proteasome and autophagy-lysosomal pathways, as well as mitochondrial dysfunction. Additionally, chemotherapy can exacerbate cachexia. This review examines the molecular mechanisms underlying cancer cachexia and discusses current therapeutic strategies, aiming to inform future research and improve treatment approaches.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189208"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189214
Brunno Gilberto Santos de Macedo , Manuela Albuquerque de Melo , Diego Antonio Pereira-Martins , João Agostinho Machado-Neto , Fabiola Traina
The gradual acquisition of genetic and epigenetic disturbances bestows malignant traits upon hematopoietic stem cells, subverting them into a founder and reservoir cell for de novo acute myeloid leukemia (AML) known as leukemic stem cells (LSC). Beyond its molecular heterogeneity, AML is also characterized by rewiring biological processes to support its onset and maintenance.
LSC were observed to inherently and actively trigger mitochondrial turnover through selective autophagic removal such that impairing the process led to cell differentiation at the expense of its stemness.
This review provides a current take on autophagy regulation mechanisms according to the current molecular characterization of the process; describes autophagy as a drug resistance mechanism, and a pivotal mechanism whereby LSC harmonize their strong reliance on mitochondrial respiration to obtain energy, and their necessity for lower internal oxidative stress to avoid exhaustion. Therefore, targeting autophagy presents a promising strategy to promote long-term remissions in AML.
{"title":"An updated outlook on autophagy mechanism and how it supports acute myeloid leukemia maintenance","authors":"Brunno Gilberto Santos de Macedo , Manuela Albuquerque de Melo , Diego Antonio Pereira-Martins , João Agostinho Machado-Neto , Fabiola Traina","doi":"10.1016/j.bbcan.2024.189214","DOIUrl":"10.1016/j.bbcan.2024.189214","url":null,"abstract":"<div><div>The gradual acquisition of genetic and epigenetic disturbances bestows malignant traits upon hematopoietic stem cells, subverting them into a founder and reservoir cell for <em>de novo</em> acute myeloid leukemia (AML) known as leukemic stem cells (LSC). Beyond its molecular heterogeneity, AML is also characterized by rewiring biological processes to support its onset and maintenance.</div><div>LSC were observed to inherently and actively trigger mitochondrial turnover through selective autophagic removal such that impairing the process led to cell differentiation at the expense of its stemness.</div><div>This review provides a current take on autophagy regulation mechanisms according to the current molecular characterization of the process; describes autophagy as a drug resistance mechanism, and a pivotal mechanism whereby LSC harmonize their strong reliance on mitochondrial respiration to obtain energy, and their necessity for lower internal oxidative stress to avoid exhaustion. Therefore, targeting autophagy presents a promising strategy to promote long-term remissions in AML.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189214"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189215
Chongmin Ren , Jia Liu , Francis J. Hornicek , Bin Yue , Zhenfeng Duan
Synovial sarcoma is a rare type of soft tissue sarcoma that primarily affects adolescents and young adults, featured by aggressive behavior and a high potential for metastasis. Genetically, synovial sarcoma is defined by the fusion oncogene SS18-SSX arising from the translocation of t(X;18)(p11;q11). SS18-SSX fusion gene is the major driver of the oncogenic event in synovial sarcoma. SS18-SSX fusion protein, while not containing any DNA-binding motifs, binds to the SWI/SNF (BAF) complex, a major epigenetic regulator, leading to the disruption of gene expression which results in tumor initiation and progression. Emerging studies on the molecular mechanisms of SS18-SSX associated signaling pathway hold promise for developments in diagnosis and treatments. Advanced diagnostic methods facilitate early and precise detection of the tumor, enabling disease monitoring and prognostic improvements. Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.
{"title":"Advances of SS18-SSX fusion gene in synovial sarcoma: Emerging novel functions and therapeutic potentials","authors":"Chongmin Ren , Jia Liu , Francis J. Hornicek , Bin Yue , Zhenfeng Duan","doi":"10.1016/j.bbcan.2024.189215","DOIUrl":"10.1016/j.bbcan.2024.189215","url":null,"abstract":"<div><div>Synovial sarcoma is a rare type of soft tissue sarcoma that primarily affects adolescents and young adults, featured by aggressive behavior and a high potential for metastasis. Genetically, synovial sarcoma is defined by the fusion oncogene SS18-SSX arising from the translocation of t(X;18)(p11;q11). SS18-SSX fusion gene is the major driver of the oncogenic event in synovial sarcoma. SS18-SSX fusion protein, while not containing any DNA-binding motifs, binds to the SWI/SNF (BAF) complex, a major epigenetic regulator, leading to the disruption of gene expression which results in tumor initiation and progression. Emerging studies on the molecular mechanisms of SS18-SSX associated signaling pathway hold promise for developments in diagnosis and treatments. Advanced diagnostic methods facilitate early and precise detection of the tumor, enabling disease monitoring and prognostic improvements. Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189215"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.bbcan.2024.189212
Yu He , Huan Li , Xueming Ju , Bo Gong
Cancer drug resistance is a major obstacle to the effectiveness of chemoradiotherapy, targeted therapy, and immunotherapy. CRISPR/Cas9 library screening has emerged as a powerful genetic screening tool with significant potential to address this challenge. This review provides an overview of the development, methodologies, and applications of CRISPR/Cas9 library screening in the study of cancer drug resistance. We explore its role in elucidating resistance mechanisms, identifying novel anticancer targets, and optimizing treatment strategies. The use of in vivo single-cell CRISPR screens is also highlighted for their capacity to reveal T-cell regulatory networks in cancer immunotherapy. Challenges in clinical translation are discussed, including off-target effects, complexities in data interpretation, and model selection. Despite these obstacles, continuous technological advancements indicate a promising future for CRISPR/Cas9 library screening in overcoming cancer drug resistance.
癌症耐药性是化放疗、靶向治疗和免疫治疗有效性的主要障碍。CRISPR/Cas9 文库筛选已成为一种强大的基因筛选工具，具有应对这一挑战的巨大潜力。本综述概述了 CRISPR/Cas9 文库筛选在癌症耐药性研究中的发展、方法和应用。我们探讨了它在阐明抗药性机制、确定新型抗癌靶点和优化治疗策略方面的作用。此外，我们还强调了体内单细胞 CRISPR 筛选在揭示癌症免疫疗法中的 T 细胞调控网络方面的作用。报告还讨论了临床转化过程中面临的挑战，包括脱靶效应、数据解读的复杂性和模型选择。尽管存在这些障碍，但技术的不断进步预示着 CRISPR/Cas9 文库筛选在克服癌症耐药性方面大有可为。
{"title":"Developing pioneering pharmacological strategies with CRISPR/Cas9 library screening to overcome cancer drug resistance","authors":"Yu He , Huan Li , Xueming Ju , Bo Gong","doi":"10.1016/j.bbcan.2024.189212","DOIUrl":"10.1016/j.bbcan.2024.189212","url":null,"abstract":"<div><div>Cancer drug resistance is a major obstacle to the effectiveness of chemoradiotherapy, targeted therapy, and immunotherapy. CRISPR/Cas9 library screening has emerged as a powerful genetic screening tool with significant potential to address this challenge. This review provides an overview of the development, methodologies, and applications of CRISPR/Cas9 library screening in the study of cancer drug resistance. We explore its role in elucidating resistance mechanisms, identifying novel anticancer targets, and optimizing treatment strategies. The use of <em>in vivo</em> single-cell CRISPR screens is also highlighted for their capacity to reveal T-cell regulatory networks in cancer immunotherapy. Challenges in clinical translation are discussed, including off-target effects, complexities in data interpretation, and model selection. Despite these obstacles, continuous technological advancements indicate a promising future for CRISPR/Cas9 library screening in overcoming cancer drug resistance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1879 6","pages":"Article 189212"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号