Pub Date : 2025-02-01DOI: 10.1016/j.bbcan.2024.189251
Eui-Jeong Han , Ji-Seon Ahn , Yu-Jin Choi , Da-Hye Kim , Jong-Soon Choi , Hea-Jong Chung
The gut microbiome, a complex community of trillions of microorganisms in the intestines, is crucial in maintaining human health. Recent advancements in microbiome research have unveiled a compelling link between the gut microbiome and cancer development and progression. Alterations in the composition and function of the gut microbiome, known as dysbiosis, have been implicated in various types of cancer, including, esophageal, liver, colon, pancreatic, and gastrointestinal. However, the specific gut microbial strains associated with the development or progression of cancers in various tissues remain largely unclear. Here, we summarize current research findings on the gut microbiome of multiple cancers. This review aims to identify key gut microbial targets that closely influence cancer development based on current research findings. To accurately evaluate the effectiveness of the gut microbiome as a clinical tool for cancer, further research is needed to explore its potential as a biomarker and therapeutic strategy.
{"title":"Exploring the gut microbiome: A potential biomarker for cancer diagnosis, prognosis, and therapy","authors":"Eui-Jeong Han , Ji-Seon Ahn , Yu-Jin Choi , Da-Hye Kim , Jong-Soon Choi , Hea-Jong Chung","doi":"10.1016/j.bbcan.2024.189251","DOIUrl":"10.1016/j.bbcan.2024.189251","url":null,"abstract":"<div><div>The gut microbiome, a complex community of trillions of microorganisms in the intestines, is crucial in maintaining human health. Recent advancements in microbiome research have unveiled a compelling link between the gut microbiome and cancer development and progression. Alterations in the composition and function of the gut microbiome, known as dysbiosis, have been implicated in various types of cancer, including, esophageal, liver, colon, pancreatic, and gastrointestinal. However, the specific gut microbial strains associated with the development or progression of cancers in various tissues remain largely unclear. Here, we summarize current research findings on the gut microbiome of multiple cancers. This review aims to identify key gut microbial targets that closely influence cancer development based on current research findings. To accurately evaluate the effectiveness of the gut microbiome as a clinical tool for cancer, further research is needed to explore its potential as a biomarker and therapeutic strategy.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189251"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886602","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189249
Lintao Xia , Xiuli Yan , Hui Zhang
Mitochondrial DNA (mtDNA), a circular double-stranded DNA located within mitochondria, plays a pivotal role in mitochondrial-induced innate immunity, particularly via the cyclic GMP-AMP synthase (cGAS)-STING pathway, which recognizes double-stranded DNA and is crucial for pathogen resistance. Recent studies elucidate the interplay among mtDNA, the cGAS-STING pathway, and neutrophil extracellular traps (NETs) in the context of cancer. mtDNA uptake by recipient cells activates the cGAS-STING pathway, while mtDNA leakage reciprocally regulates NET release, amplifying inflammation and promoting NETosis, a mechanism of tumor cell death. Autophagy modulates these processes by clearing damaged mitochondria and degrading cGAS, thus preventing mtDNA recognition. Tumor microenvironmental factors, such as metabolic reprogramming and lipid accumulation, induce mitochondrial stress, ROS production, and further mtDNA leakage. This review explores strategies in cancer drug development that leverage mtDNA leakage to activate the cGAS-STING pathway, potentially converting ‘cold tumors’ into ‘hot tumors,’ while discussing advancements in targeted therapies and proposing new research methodologies.
{"title":"Mitochondrial DNA-activated cGAS-STING pathway in cancer: Mechanisms and therapeutic implications","authors":"Lintao Xia , Xiuli Yan , Hui Zhang","doi":"10.1016/j.bbcan.2024.189249","DOIUrl":"10.1016/j.bbcan.2024.189249","url":null,"abstract":"<div><div>Mitochondrial DNA (mtDNA), a circular double-stranded DNA located within mitochondria, plays a pivotal role in mitochondrial-induced innate immunity, particularly via the cyclic GMP-AMP synthase (cGAS)-STING pathway, which recognizes double-stranded DNA and is crucial for pathogen resistance. Recent studies elucidate the interplay among mtDNA, the cGAS-STING pathway, and neutrophil extracellular traps (NETs) in the context of cancer. mtDNA uptake by recipient cells activates the cGAS-STING pathway, while mtDNA leakage reciprocally regulates NET release, amplifying inflammation and promoting NETosis, a mechanism of tumor cell death. Autophagy modulates these processes by clearing damaged mitochondria and degrading cGAS, thus preventing mtDNA recognition. Tumor microenvironmental factors, such as metabolic reprogramming and lipid accumulation, induce mitochondrial stress, ROS production, and further mtDNA leakage. This review explores strategies in cancer drug development that leverage mtDNA leakage to activate the cGAS-STING pathway, potentially converting ‘cold tumors’ into ‘hot tumors,’ while discussing advancements in targeted therapies and proposing new research methodologies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189249"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866304","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 : 2025-02-01DOI: 10.1016/j.bbcan.2025.189260
Lianglong Chen, Yaning Che, Chao Huang
SUMOylation is a protein modification process that involves the covalent attachment of a small ubiquitin-like modifier (SUMO) to a specific lysine residue on the target protein. This modification can influence the function, localization, stability, and interactions of proteins, thereby regulating various cellular processes. Altering the SUMOylation of certain proteins is expected to be a potential approach for treating specific cancers and diseases. Among these, SENP3 can affect target proteins by regulating the deSUMOylation process, which in turn influences the transcriptional activity of downstream genes, playing a role in either promoting or inhibiting cancer. SENP3 regulates the SUMO status of proteins in numerous signaling pathways, modulating the activity of specific signaling molecules to impact cellular responses and tumor progression. Additionally, SENP3 promotes cell growth and division by deSUMOylating key cyclins. In the context of DNA repair, SENP3 regulates the activity of proteins associated with DNA repair by deSUMOylating repair factors, thereby enhancing DNA repair and maintaining genome stability. Furthermore, SENP3 has specific functions in various other diseases. The complex roles of SENP3 indicate its potential as both a therapeutic target and a biomarker.
{"title":"SENP3: Cancers and diseases","authors":"Lianglong Chen, Yaning Che, Chao Huang","doi":"10.1016/j.bbcan.2025.189260","DOIUrl":"10.1016/j.bbcan.2025.189260","url":null,"abstract":"<div><div>SUMOylation is a protein modification process that involves the covalent attachment of a small ubiquitin-like modifier (SUMO) to a specific lysine residue on the target protein. This modification can influence the function, localization, stability, and interactions of proteins, thereby regulating various cellular processes. Altering the SUMOylation of certain proteins is expected to be a potential approach for treating specific cancers and diseases. Among these, SENP3 can affect target proteins by regulating the deSUMOylation process, which in turn influences the transcriptional activity of downstream genes, playing a role in either promoting or inhibiting cancer. SENP3 regulates the SUMO status of proteins in numerous signaling pathways, modulating the activity of specific signaling molecules to impact cellular responses and tumor progression. Additionally, SENP3 promotes cell growth and division by deSUMOylating key cyclins. In the context of DNA repair, SENP3 regulates the activity of proteins associated with DNA repair by deSUMOylating repair factors, thereby enhancing DNA repair and maintaining genome stability. Furthermore, SENP3 has specific functions in various other diseases. The complex roles of SENP3 indicate its potential as both a therapeutic target and a biomarker.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189260"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967534","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189252
Shuangsi Liao , Kai Kang , Zhuoran Yao , You Lu
The nervous system plays a vital role throughout the entire lifecycle and it may regulate the formation, development and metastasis of tumors. Small cell lung cancer is a typical neuroendocrine tumor, and it is naturally equipped with neurotropism. In this review, we firstly summarize current preclinical and clinical evidence to demonstrate the reciprocal crosstalk among the nervous system, tumor, and tumor microenvironment in various ways, including neurotransmitter-receptor pathways, innervations of nerve fibers, different types of synapse formation by neurons, astrocytes, and cancer cells, neoneurogenesis. Futherly, we emphasize how the nervous system interacts with small cell lung cancer and discuss the limitations of current research methods for examining the interactions. We propose that integrating neuroscience, development biology, and tumor biology can be a promising direction to provide new insights into development and metastasis of small cell lung cancer and raise some novel treatment strategies.
{"title":"Nervous system contributions to small cell lung cancer: Lessons from diverse oncological studies","authors":"Shuangsi Liao , Kai Kang , Zhuoran Yao , You Lu","doi":"10.1016/j.bbcan.2024.189252","DOIUrl":"10.1016/j.bbcan.2024.189252","url":null,"abstract":"<div><div>The nervous system plays a vital role throughout the entire lifecycle and it may regulate the formation, development and metastasis of tumors. Small cell lung cancer is a typical neuroendocrine tumor, and it is naturally equipped with neurotropism. In this review, we firstly summarize current preclinical and clinical evidence to demonstrate the reciprocal crosstalk among the nervous system, tumor, and tumor microenvironment in various ways, including neurotransmitter-receptor pathways, innervations of nerve fibers, different types of synapse formation by neurons, astrocytes, and cancer cells, neoneurogenesis. Futherly, we emphasize how the nervous system interacts with small cell lung cancer and discuss the limitations of current research methods for examining the interactions. We propose that integrating neuroscience, development biology, and tumor biology can be a promising direction to provide new insights into development and metastasis of small cell lung cancer and raise some novel treatment strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189252"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900622","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189230
Yuting Wang M.D. , Jing Han M.D./Ph.D. , Yongxue Zhu M.D. , Naisi Huang M.D. , Ning Qu M.D. Ph.D.
Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy with a poor prognosis, particularly when diagnosed at advanced stages. Despite progress in surgical, chemotherapeutic, and radiotherapeutic interventions, the five-year survival rate remains low due to high rates of recurrence and therapeutic resistance. This review explores recent advances in therapeutic strategies for HNSCC, focusing on targeted therapies, immunotherapy, and innovative drug delivery systems.
Targeted therapies, such as EGFR inhibitors and PI3K/AKT/mTOR pathway inhibitors, offer promising options for overcoming HNSCC, though resistance challenges persist. Emerging treatments, including dual-target inhibitors and personalized therapeutic approaches, show potential in addressing these limitations. Immunotherapy, particularly PD-1/PD-L1 blockade, has achieved positive outcomes in a subset of patients, though overall response rates remain modest. Strategies aimed at enhancing immune responses, such as combination therapies and nanotechnology-based drug delivery systems, are actively being investigated to improve efficacy. This review also underscores the critical role of the tumor microenvironment and epithelial-mesenchymal transition (EMT) in HNSCC progression and therapeutic resistance. Novel approaches, including smart drug delivery systems utilizing nanotechnology and immune modulation, are opening new avenues for more personalized and effective treatments. Ongoing interdisciplinary research into molecular targets and advanced drug delivery techniques holds great promise for significantly improving patient outcomes in HNSCC.
{"title":"New advances in the therapeutic strategy of head and neck squamous cell carcinoma: A review of latest therapies and cutting-edge research","authors":"Yuting Wang M.D. , Jing Han M.D./Ph.D. , Yongxue Zhu M.D. , Naisi Huang M.D. , Ning Qu M.D. Ph.D.","doi":"10.1016/j.bbcan.2024.189230","DOIUrl":"10.1016/j.bbcan.2024.189230","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy with a poor prognosis, particularly when diagnosed at advanced stages. Despite progress in surgical, chemotherapeutic, and radiotherapeutic interventions, the five-year survival rate remains low due to high rates of recurrence and therapeutic resistance. This review explores recent advances in therapeutic strategies for HNSCC, focusing on targeted therapies, immunotherapy, and innovative drug delivery systems.</div><div>Targeted therapies, such as EGFR inhibitors and PI3K/AKT/mTOR pathway inhibitors, offer promising options for overcoming HNSCC, though resistance challenges persist. Emerging treatments, including dual-target inhibitors and personalized therapeutic approaches, show potential in addressing these limitations. Immunotherapy, particularly PD-1/PD-L1 blockade, has achieved positive outcomes in a subset of patients, though overall response rates remain modest. Strategies aimed at enhancing immune responses, such as combination therapies and nanotechnology-based drug delivery systems, are actively being investigated to improve efficacy. This review also underscores the critical role of the tumor microenvironment and epithelial-mesenchymal transition (EMT) in HNSCC progression and therapeutic resistance. Novel approaches, including smart drug delivery systems utilizing nanotechnology and immune modulation, are opening new avenues for more personalized and effective treatments. Ongoing interdisciplinary research into molecular targets and advanced drug delivery techniques holds great promise for significantly improving patient outcomes in HNSCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189230"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752432","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189255
Takeyuki Kono, Hiroyuki Ozawa
The DNA damage response (DDR) is an essential mechanism for maintaining genomic stability. Although DDR-targeted therapeutic strategies are being developed in several familial cancers, evaluation of their utility in head and neck squamous cell cancer (HNSCC) is lagging.
This review briefly summarizes the mechanisms of DDR and the current knowledge on discovering DDR-related predictive biomarkers in HNSCC. This review also presents novel therapeutic strategies targeting DDR pathways for HNSCC based on the synthetic lethal concept. The combination of DDR inhibitors with cytotoxic treatments such as radiotherapy, chemotherapy, and immune checkpoint inhibitors is being evaluated, and several clinical trials are ongoing in patients with HNSCC. While DDR inhibitors are considered promising treatment options, resistance to these drugs is frequently observed, and their mechanisms are currently active research areas. A better understanding of the correlation between DDR pathways and cancer biology provides new therapeutic strategies for personalized medicine in HNSCC.
{"title":"A comprehensive review of current therapeutic strategies in cancers targeting DNA damage response mechanisms in head and neck squamous cell cancer","authors":"Takeyuki Kono, Hiroyuki Ozawa","doi":"10.1016/j.bbcan.2024.189255","DOIUrl":"10.1016/j.bbcan.2024.189255","url":null,"abstract":"<div><div>The DNA damage response (DDR) is an essential mechanism for maintaining genomic stability. Although DDR-targeted therapeutic strategies are being developed in several familial cancers, evaluation of their utility in head and neck squamous cell cancer (HNSCC) is lagging.</div><div>This review briefly summarizes the mechanisms of DDR and the current knowledge on discovering DDR-related predictive biomarkers in HNSCC. This review also presents novel therapeutic strategies targeting DDR pathways for HNSCC based on the synthetic lethal concept. The combination of DDR inhibitors with cytotoxic treatments such as radiotherapy, chemotherapy, and immune checkpoint inhibitors is being evaluated, and several clinical trials are ongoing in patients with HNSCC. While DDR inhibitors are considered promising treatment options, resistance to these drugs is frequently observed, and their mechanisms are currently active research areas. A better understanding of the correlation between DDR pathways and cancer biology provides new therapeutic strategies for personalized medicine in HNSCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189255"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924171","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189245
Lifei Jiang , Yibin Kang
Cells are compartmentalized into different organelles to ensure precise spatial temporal control and efficient operation of cellular processes. Membraneless organelles, also known as biomolecular condensates, are emerging as previously underappreciated ways of organizing cellular functions. Condensates allow local concentration of protein, RNA, or DNA molecules with shared functions, thus facilitating spatiotemporal control of biochemical reactions spanning a range of cellular processes. Studies discussed herein have shown that aberrant formation of condensates is associated with various diseases such as cancers. Here, we summarize how condensates mechanistically contribute to malignancy-related cellular processes, including genomic instability, epigenetic rewiring, oncogenic transcriptional activation, and signaling. An improved understanding of condensate formation and dissolution will enable development of new cancer therapies. Finally, we address the remaining challenges in the field and suggest future efforts to better integrate condensates into cancer research.
细胞被分隔成不同的细胞器，以确保精确的时空控制和细胞过程的高效运行。无膜细胞器，也称为生物分子凝聚体，正在成为以前未被重视的细胞功能组织方式。凝聚体允许具有共享功能的蛋白质、RNA 或 DNA 分子在局部聚集，从而促进了对一系列细胞过程的生化反应的时空控制。本文讨论的研究表明，凝集素的异常形成与癌症等多种疾病有关。在此，我们将总结凝集素是如何从机理上促进与恶性肿瘤相关的细胞过程的，包括基因组不稳定性、表观遗传改组、致癌转录激活和信号转导。加深对凝集物形成和溶解的了解将有助于开发新的癌症疗法。最后，我们探讨了该领域仍然存在的挑战，并提出了今后如何更好地将凝结物纳入癌症研究的建议。
{"title":"Biomolecular condensates: A new lens on cancer biology","authors":"Lifei Jiang , Yibin Kang","doi":"10.1016/j.bbcan.2024.189245","DOIUrl":"10.1016/j.bbcan.2024.189245","url":null,"abstract":"<div><div>Cells are compartmentalized into different organelles to ensure precise spatial temporal control and efficient operation of cellular processes. Membraneless organelles, also known as biomolecular condensates, are emerging as previously underappreciated ways of organizing cellular functions. Condensates allow local concentration of protein, RNA, or DNA molecules with shared functions, thus facilitating spatiotemporal control of biochemical reactions spanning a range of cellular processes. Studies discussed herein have shown that aberrant formation of condensates is associated with various diseases such as cancers. Here, we summarize how condensates mechanistically contribute to malignancy-related cellular processes, including genomic instability, epigenetic rewiring, oncogenic transcriptional activation, and signaling. An improved understanding of condensate formation and dissolution will enable development of new cancer therapies. Finally, we address the remaining challenges in the field and suggest future efforts to better integrate condensates into cancer research.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189245"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831174","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 : 2025-02-01DOI: 10.1016/j.bbcan.2024.189246
Xin-Pan Chen , Zi-Tao Yang , Shang-Xin Yang , En-Min Li , Lei Xie
P21-activated kinases (PAKs) are crucial regulators within cellular signaling pathways and have been implicated in a range of human diseases, including cancer. Among the PAK family, PAK2 is widely expressed across various tissues and has emerged as a significant driver of cancer progression. However, systematic studies on PAK2 remain limited. This review provides a comprehensive overview of PAK2's role in cancer, focusing on its involvement in processes such as angiogenesis, metastasis, cell survival, metabolism, immune response, and drug resistance. We also explore its function in key cancer signaling pathways and the potential of small-molecule inhibitors targeting PAK2 for therapeutic purposes. Despite promising preclinical data, no PAK2 inhibitors have reached clinical practice, underscoring challenges related to their specificity and therapeutic application. This review highlights the biological significance of PAK2 in cancer and its interactions with critical signaling pathways, offering valuable insights for future research. We also discuss the major obstacles in developing PAK inhibitors and propose strategies to overcome these barriers, paving the way for their clinical translation.
{"title":"PAK2 as a therapeutic target in cancer: Mechanisms, challenges, and future perspectives","authors":"Xin-Pan Chen , Zi-Tao Yang , Shang-Xin Yang , En-Min Li , Lei Xie","doi":"10.1016/j.bbcan.2024.189246","DOIUrl":"10.1016/j.bbcan.2024.189246","url":null,"abstract":"<div><div>P21-activated kinases (PAKs) are crucial regulators within cellular signaling pathways and have been implicated in a range of human diseases, including cancer. Among the PAK family, PAK2 is widely expressed across various tissues and has emerged as a significant driver of cancer progression. However, systematic studies on PAK2 remain limited. This review provides a comprehensive overview of PAK2's role in cancer, focusing on its involvement in processes such as angiogenesis, metastasis, cell survival, metabolism, immune response, and drug resistance. We also explore its function in key cancer signaling pathways and the potential of small-molecule inhibitors targeting PAK2 for therapeutic purposes. Despite promising preclinical data, no PAK2 inhibitors have reached clinical practice, underscoring challenges related to their specificity and therapeutic application. This review highlights the biological significance of PAK2 in cancer and its interactions with critical signaling pathways, offering valuable insights for future research. We also discuss the major obstacles in developing PAK inhibitors and propose strategies to overcome these barriers, paving the way for their clinical translation.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189246"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856993","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 : 2025-02-01DOI: 10.1016/j.bbcan.2025.189275
Szilárd-Krisztián Belényesi , Sean Patmore , Lorraine O'Driscoll
Extracellular vesicles (EVs), tiny packages of information released by cells, are well established as being involved in unwanted cell-to-cell communication in cancer. EVs from cancer cells have been associated with the spread of drug resistance, immune suppression, and metastasis. Additional to cancer cells, the tumour microenvironment (TME) involves many cell types -including immune cells, fibroblasts, and endothelial cells, each of which has a potential role in how tumours grow, spread, and respond (or otherwise) to therapy. This review collates and distils research developments regarding the role of EVs in multi-way communication between cells in the TME. Further research including tailored clinical studies are now warranted to determine how best to prevent this extensive adverse communication occurring and/or how best to exploit it for biomarker discovery and as a therapeutic approach, in the interest of patients and also for economic benefit.
{"title":"Extracellular vesicles and the tumour microenvironment","authors":"Szilárd-Krisztián Belényesi , Sean Patmore , Lorraine O'Driscoll","doi":"10.1016/j.bbcan.2025.189275","DOIUrl":"10.1016/j.bbcan.2025.189275","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), tiny packages of information released by cells, are well established as being involved in unwanted cell-to-cell communication in cancer. EVs from cancer cells have been associated with the spread of drug resistance, immune suppression, and metastasis. Additional to cancer cells, the tumour microenvironment (TME) involves many cell types -including immune cells, fibroblasts, and endothelial cells, each of which has a potential role in how tumours grow, spread, and respond (or otherwise) to therapy. This review collates and distils research developments regarding the role of EVs in multi-way communication between cells in the TME. Further research including tailored clinical studies are now warranted to determine how best to prevent this extensive adverse communication occurring and/or how best to exploit it for biomarker discovery and as a therapeutic approach, in the interest of patients and also for economic benefit.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 2","pages":"Article 189275"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124159","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}
Brain metastasis stands as a leading contributor to mortality in lung cancer patients, yet the intricate mechanism underlying this phenomenon remains elusive. This underscores the need for robust preclinical models and effective treatment strategies. Emerging as viable in vitro models that closely replicate actual tumors, three-dimensional culture systems, particularly organoids derived from non-malignant cells or cancer organoids, have emerged as promising avenues. This review delves into the forefronts of fundamental research and clinical applications focused on lung cancer brain metastasis-derived organoids, highlighting current challenges and delineating prospects. These studies offer tremendous potential for clinical application despite being in nascent status.
{"title":"Organoids in lung cancer brain metastasis: Foundational research, clinical translation, and prospective outlooks","authors":"Mei Zheng , Jialin Qu , Dongxi Xiang , Ligang Xing","doi":"10.1016/j.bbcan.2024.189235","DOIUrl":"10.1016/j.bbcan.2024.189235","url":null,"abstract":"<div><div>Brain metastasis stands as a leading contributor to mortality in lung cancer patients, yet the intricate mechanism underlying this phenomenon remains elusive. This underscores the need for robust preclinical models and effective treatment strategies. Emerging as viable in vitro models that closely replicate actual tumors, three-dimensional culture systems, particularly organoids derived from non-malignant cells or cancer organoids, have emerged as promising avenues. This review delves into the forefronts of fundamental research and clinical applications focused on lung cancer brain metastasis-derived organoids, highlighting current challenges and delineating prospects. These studies offer tremendous potential for clinical application despite being in nascent status.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 1","pages":"Article 189235"},"PeriodicalIF":9.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796466","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}
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