Pub Date : 2025-12-24DOI: 10.1016/j.bbcan.2025.189522
Yingyi Liu , Sze-Nga Wong , Aiping Lyu , Joshua Ka-Shun Ko
Rac1 belongs to the Rac subfamily under the Rho family of GTPases. As an effector of K-Ras protein encoded by the KRAS gene, Rac1 activation plays a key role in KRAS-driven cancer development and is largely involved in the promotion of cell migration and chemoresistance in pancreatic cancer. Evidence has indicated that pancreas-specific knockdown of Rac1 may prevent disease progression, while pharmacological inhibition of Rac1 can exert strong anti-cancer effects. In this review, we have discussed the relationship between Rac1 and neoplastic development, whereas different treatment schemes on pancreatic cancer through modulation of Rac1 during chemotherapy will be emphasized. Furthermore, we elaborated on contemporary studies of the Rac1 inhibitor EHop-016 and related compounds that have shown anti-tumor capability in preclinical models and their potential clinical applications. Exploration on the therapeutic prospect of phytochemicals derived from natural products capable of inhibiting cancer cell growth and disease progression by modulating Rac1 has been envisaged. Lastly, the complex correlation between Rac1 signaling and autophagy during treatment of pancreatic cancer by the novel phytochemical isoliquiritigenin would be introduced.
{"title":"Advancement in preclinical development of cancer treatment agents through modulation of Rac1: From EHop-016 to natural products","authors":"Yingyi Liu , Sze-Nga Wong , Aiping Lyu , Joshua Ka-Shun Ko","doi":"10.1016/j.bbcan.2025.189522","DOIUrl":"10.1016/j.bbcan.2025.189522","url":null,"abstract":"<div><div>Rac1 belongs to the Rac subfamily under the Rho family of GTPases. As an effector of K-Ras protein encoded by the <em>KRAS</em> gene, Rac1 activation plays a key role in KRAS-driven cancer development and is largely involved in the promotion of cell migration and chemoresistance in pancreatic cancer. Evidence has indicated that pancreas-specific knockdown of <em>Rac1</em> may prevent disease progression, while pharmacological inhibition of Rac1 can exert strong anti-cancer effects. In this review, we have discussed the relationship between Rac1 and neoplastic development, whereas different treatment schemes on pancreatic cancer through modulation of Rac1 during chemotherapy will be emphasized. Furthermore, we elaborated on contemporary studies of the Rac1 inhibitor EHop-016 and related compounds that have shown anti-tumor capability in preclinical models and their potential clinical applications. Exploration on the therapeutic prospect of phytochemicals derived from natural products capable of inhibiting cancer cell growth and disease progression by modulating Rac1 has been envisaged. Lastly, the complex correlation between Rac1 signaling and autophagy during treatment of pancreatic cancer by the novel phytochemical isoliquiritigenin would be introduced.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189522"},"PeriodicalIF":9.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844664","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 : 2025-12-23DOI: 10.1016/j.bbcan.2025.189518
Shu Cui , Fan Guan , Xuetong Li , Xinmiao Long , Minghua Wu
Glioblastoma (GBM) remains one of the most aggressive and lethal brain tumors in adults, characterized by extensive heterogeneity, robust therapeutic resistance, and a dismal prognosis despite maximal surgical resection, radiotherapy, and chemotherapy. A defining hallmark of GBM is its complex tumor microenvironment (TME), a dynamic ecosystem comprising immune cells, vascular networks, extracellular matrix, and various stromal components that collectively drive tumor progression and therapeutic evasion. Within this intricate niche, astrocytes, traditionally regarded as passive support cells in the central nervous system (CNS), have emerged as pivotal orchestrators of GBM pathogenesis. These cells undergo profound phenotypic reprogramming upon interaction with GBM cells, adopting diverse roles that encompass metabolic support, immune suppression, promotion of invasive growth, and induction of therapy resistance. Regulated by key signaling pathways and influenced by GBM-derived exosomes, blood-brain barrier disruption, and tumor-associated hypoxia, astrocytes exhibit remarkable plasticity and heterogeneity, including putative subtypes such as metabolic homeostasis, immune-inflammatory reactive, gliomagenic, and senescence-associated subtypes. Their ability to shape the TME through immunosuppressive axis activation, energy support, metabolic crosstalk, and intercellular communication via tunneling nanotubes (TNTs) and extracellular vesicles (EVs) underscores their critical role in GBM biology. This review focuses on the multifaceted contributions of astrocytes within the GBM microenvironment, exploring their phenotypic diversity, regulatory mechanisms, therapeutic potential as emerging targets to dismantle the pro-tumor niche as well as to improve patient outcomes and advances in technologies for investigating astrocytes in GBM.
{"title":"Astrocytes in glioblastoma tumor microenvironment","authors":"Shu Cui , Fan Guan , Xuetong Li , Xinmiao Long , Minghua Wu","doi":"10.1016/j.bbcan.2025.189518","DOIUrl":"10.1016/j.bbcan.2025.189518","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most aggressive and lethal brain tumors in adults, characterized by extensive heterogeneity, robust therapeutic resistance, and a dismal prognosis despite maximal surgical resection, radiotherapy, and chemotherapy. A defining hallmark of GBM is its complex tumor microenvironment (TME), a dynamic ecosystem comprising immune cells, vascular networks, extracellular matrix, and various stromal components that collectively drive tumor progression and therapeutic evasion. Within this intricate niche, astrocytes, traditionally regarded as passive support cells in the central nervous system (CNS), have emerged as pivotal orchestrators of GBM pathogenesis. These cells undergo profound phenotypic reprogramming upon interaction with GBM cells, adopting diverse roles that encompass metabolic support, immune suppression, promotion of invasive growth, and induction of therapy resistance. Regulated by key signaling pathways and influenced by GBM-derived exosomes, blood-brain barrier disruption, and tumor-associated hypoxia, astrocytes exhibit remarkable plasticity and heterogeneity, including putative subtypes such as metabolic homeostasis, immune-inflammatory reactive, gliomagenic, and senescence-associated subtypes. Their ability to shape the TME through immunosuppressive axis activation, energy support, metabolic crosstalk, and intercellular communication via tunneling nanotubes (TNTs) and extracellular vesicles (EVs) underscores their critical role in GBM biology. This review focuses on the multifaceted contributions of astrocytes within the GBM microenvironment, exploring their phenotypic diversity, regulatory mechanisms, therapeutic potential as emerging targets to dismantle the pro-tumor niche as well as to improve patient outcomes and advances in technologies for investigating astrocytes in GBM.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189518"},"PeriodicalIF":9.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835569","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 : 2025-12-23DOI: 10.1016/j.bbcan.2025.189521
Ting Yang, Rui Qian, Xuanxuan Sun, Xin Hu, Youzhong Wan
Splicing factor 3B subunit 1 (SF3B1), a core component of the U2 small nuclear ribonucleoprotein, has key functions in precursor messenger RNA (pre-mRNA) splicing and regulates gene expression by recognizing branch point sequences and coordinating spliceosome assembly. Mutations of SF3B1 have been identified as high-frequency drivers in various tumor types. These include hotspot mutations such as K700E, which reshape the splicing factor network via abnormal interactions with SUGP1, DHX15, etc., resulting in activation of latent splicing sites. These changes in turn affect genes involved in RNA metabolism and the cell cycle and genomic stability, thereby triggering the downstream NF-κB, AKT, and p53 pathways to promote tumorigenesis. Clinically, SF3B1 mutations occur in both hematological tumors (as in myelodysplastic syndrome) and solid tumors (such as breast cancer). Mutation-mediated splicing abnormalities thus represent targets for new therapeutic agents such as spliceosome inhibitor pladienolide B. However, although studies have advanced our understanding of these abnormalities from basic splicing changes to effects on signaling networks and potential clinical translation, various aspects need further exploration; these include mutation-specific functional heterogeneity, interactions with the tumor microenvironment, and mechanisms of drug resistance. This review systematically summarizes the functions of SF3B1 mutations and their underlying molecular mechanisms in spliceosome-driven tumorigenesis, with the aim of providing a framework for better understanding of this process, as well as discussing prospects for new precision medicine diagnostic and treatment strategies.
{"title":"SF3B1 mutations in spliceosome-driven tumorigenesis: From splicing dysregulation to signaling network rewiring and therapeutic targeting","authors":"Ting Yang, Rui Qian, Xuanxuan Sun, Xin Hu, Youzhong Wan","doi":"10.1016/j.bbcan.2025.189521","DOIUrl":"10.1016/j.bbcan.2025.189521","url":null,"abstract":"<div><div>Splicing factor 3B subunit 1 (SF3B1), a core component of the U2 small nuclear ribonucleoprotein, has key functions in precursor messenger RNA (pre-mRNA) splicing and regulates gene expression by recognizing branch point sequences and coordinating spliceosome assembly. Mutations of <em>SF3B1</em> have been identified as high-frequency drivers in various tumor types. These include hotspot mutations such as K700E, which reshape the splicing factor network via abnormal interactions with SUGP1, DHX15, etc., resulting in activation of latent splicing sites. These changes in turn affect genes involved in RNA metabolism and the cell cycle and genomic stability, thereby triggering the downstream NF-κB, AKT, and p53 pathways to promote tumorigenesis. Clinically, <em>SF3B1</em> mutations occur in both hematological tumors (as in myelodysplastic syndrome) and solid tumors (such as breast cancer). Mutation-mediated splicing abnormalities thus represent targets for new therapeutic agents such as spliceosome inhibitor pladienolide B. However, although studies have advanced our understanding of these abnormalities from basic splicing changes to effects on signaling networks and potential clinical translation, various aspects need further exploration; these include mutation-specific functional heterogeneity, interactions with the tumor microenvironment, and mechanisms of drug resistance. This review systematically summarizes the functions of <em>SF3B1</em> mutations and their underlying molecular mechanisms in spliceosome-driven tumorigenesis, with the aim of providing a framework for better understanding of this process, as well as discussing prospects for new precision medicine diagnostic and treatment strategies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189521"},"PeriodicalIF":9.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835591","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}
Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has revolutionized the treatment of B-cell malignancies. One of the critical factors influencing CAR-T efficacy and durability is the costimulatory domain, with 4-1BB and CD28 emerging as the two dominant signaling platforms. While CD28-based CAR-T cells exhibit strong initial potency and rapid expansion, 4-1BB-based CAR-T cells demonstrate greater persistence and long-term efficacy. However, resistance to CAR-T therapy remains a significant challenge. Tumor cells develop a variety of mechanisms to evade immune surveillance, including CD19 antigen escape due to epigenetic factors or genetic aberrations of the CD19 gene. This review article summarizes the mechanistic differences between both costimulatory domains, their impact on clinical outcomes, and how they might influence resistance occurrence. By dissecting the battle of potency and the race of persistence, we provide insights into the evolving landscape of CAR-T therapy for B-cell malignancies.
{"title":"The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies","authors":"Marta Krawczyk , Magdalena Drużyńska , Emilia Bednarska , Magdalena Winiarska","doi":"10.1016/j.bbcan.2025.189519","DOIUrl":"10.1016/j.bbcan.2025.189519","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has revolutionized the treatment of B-cell malignancies. One of the critical factors influencing CAR-T efficacy and durability is the costimulatory domain, with 4-1BB and CD28 emerging as the two dominant signaling platforms. While CD28-based CAR-T cells exhibit strong initial potency and rapid expansion, 4-1BB-based CAR-T cells demonstrate greater persistence and long-term efficacy. However, resistance to CAR-T therapy remains a significant challenge. Tumor cells develop a variety of mechanisms to evade immune surveillance, including CD19 antigen escape due to epigenetic factors or genetic aberrations of the <em>CD19</em> gene. This review article summarizes the mechanistic differences between both costimulatory domains, their impact on clinical outcomes, and how they might influence resistance occurrence. By dissecting the battle of potency and the race of persistence, we provide insights into the evolving landscape of CAR-T therapy for B-cell malignancies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189519"},"PeriodicalIF":9.7,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812427","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 : 2025-12-18DOI: 10.1016/j.bbcan.2025.189517
Zilong Zhang, Xiaoping Chen, Bixiang Zhang, Wanguang Zhang, Ze-yang Ding, on behalf of the Expert Group on Portal Hypertension of the Chinese College of Surgeons (CCS), Chinese Medical Doctor Association (CMDA)
Hepatocellular carcinoma (HCC) arising on a background of fibrosis has fundamental mechanistic and clinical differences compared to HCC that arises in a non-fibrotic liver. The fibrotic microenvironment is characterized by extracellular matrix (ECM) remodeling, dynamic interactions with immune and stromal cells, and activation of hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs). Recent multi-omics analyses have demonstrated that these fibrotic niches dynamically promote hepatocarcinogenesis, metastasis and immune evasion. Several therapeutic strategies targeting fibrosis have improved HCC outcomes in clinical trials. These advances have facilitated an understanding of the complex mechanisms underlying fibrosis-driven HCC and are helping to optimize therapeutic prescriptions. This review synthesizes recent advances in understanding the role of fibrosis in hepatocarcinogenesis, aggressiveness, and metastasis; decodes how stromal-immune crosstalk defines immune escape through the fibrosis-driven ‘3C’ immune evasion framework; and links mechanistic insights into fibrosis-driven HCC with emerging theranostic strategies. We emphasize that targeting fibrosis-driven oncogenic mechanisms may enhance the therapeutic efficacy in HCC, thus providing a scientific foundation for rationalizing this approach as a viable strategy against both liver fibrosis and HCC.
{"title":"Fibrosis-driven hepatocarcinogenesis, metastasis and immune evasion: Mechanisms and therapeutic targets","authors":"Zilong Zhang, Xiaoping Chen, Bixiang Zhang, Wanguang Zhang, Ze-yang Ding, on behalf of the Expert Group on Portal Hypertension of the Chinese College of Surgeons (CCS), Chinese Medical Doctor Association (CMDA)","doi":"10.1016/j.bbcan.2025.189517","DOIUrl":"10.1016/j.bbcan.2025.189517","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) arising on a background of fibrosis has fundamental mechanistic and clinical differences compared to HCC that arises in a non-fibrotic liver. The fibrotic microenvironment is characterized by extracellular matrix (ECM) remodeling, dynamic interactions with immune and stromal cells, and activation of hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs). Recent multi-omics analyses have demonstrated that these fibrotic niches dynamically promote hepatocarcinogenesis, metastasis and immune evasion. Several therapeutic strategies targeting fibrosis have improved HCC outcomes in clinical trials. These advances have facilitated an understanding of the complex mechanisms underlying fibrosis-driven HCC and are helping to optimize therapeutic prescriptions. This review synthesizes recent advances in understanding the role of fibrosis in hepatocarcinogenesis, aggressiveness, and metastasis; decodes how stromal-immune crosstalk defines immune escape through the fibrosis-driven ‘3C’ immune evasion framework; and links mechanistic insights into fibrosis-driven HCC with emerging theranostic strategies. We emphasize that targeting fibrosis-driven oncogenic mechanisms may enhance the therapeutic efficacy in HCC, thus providing a scientific foundation for rationalizing this approach as a viable strategy against both liver fibrosis and HCC.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189517"},"PeriodicalIF":9.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800837","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 : 2025-12-16DOI: 10.1016/j.bbcan.2025.189515
Wen Zheng , Wenjie Chen , Gyorgy Hutvagner , Laura Rangel-Sanchez , Wei Deng
Messenger RNA (mRNA) vaccines have become a transformative approach in immunotherapy and have attracted significant attention owing to their unprecedented success in controlling COVID-19. With their ability to flexibly and specifically encode tumour-associated antigens, along with their favorable safety profiles and scalable manufacturing, mRNA vaccines represent a highly promising platform for cancer treatment. Breast cancer is a heterogeneous disease and many of its subtypes are immunologically cold tumours, which has limited the progress of immunotherapy in this field. Recent studies have highlighted the potential of mRNA vaccines to reshape the tumour immune microenvironment in breast cancer. These vaccines can enhance antigen presentation, activate T cell responses, and convert immunologically cold tumours into immune-active ones. This review provides a comprehensive overview of recent advances in mRNA vaccine development for breast cancer with a focus on antigen selection, mRNA design, and delivery strategies. It also examines findings from both preclinical and clinical studies as well as recent progress in industrial development. Finally, we discuss the current challenges hindering the clinical translation and ethical considerations of mRNA vaccine technology and propose future directions to advance mRNA vaccine-based therapies for breast cancer.
{"title":"Advancements in breast cancer mRNA vaccines: Current development and future prospects","authors":"Wen Zheng , Wenjie Chen , Gyorgy Hutvagner , Laura Rangel-Sanchez , Wei Deng","doi":"10.1016/j.bbcan.2025.189515","DOIUrl":"10.1016/j.bbcan.2025.189515","url":null,"abstract":"<div><div>Messenger RNA (mRNA) vaccines have become a transformative approach in immunotherapy and have attracted significant attention owing to their unprecedented success in controlling COVID-19. With their ability to flexibly and specifically encode tumour-associated antigens, along with their favorable safety profiles and scalable manufacturing, mRNA vaccines represent a highly promising platform for cancer treatment. Breast cancer is a heterogeneous disease and many of its subtypes are immunologically cold tumours, which has limited the progress of immunotherapy in this field. Recent studies have highlighted the potential of mRNA vaccines to reshape the tumour immune microenvironment in breast cancer. These vaccines can enhance antigen presentation, activate T cell responses, and convert immunologically cold tumours into immune-active ones. This review provides a comprehensive overview of recent advances in mRNA vaccine development for breast cancer with a focus on antigen selection, mRNA design, and delivery strategies. It also examines findings from both preclinical and clinical studies as well as recent progress in industrial development. Finally, we discuss the current challenges hindering the clinical translation and ethical considerations of mRNA vaccine technology and propose future directions to advance mRNA vaccine-based therapies for breast cancer.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189515"},"PeriodicalIF":9.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784008","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 : 2025-12-16DOI: 10.1016/j.bbcan.2025.189516
Xiaoran Zhen , Dongyan Zhang , Dongbao Li , Bo Fu , Keyi Li
Oral squamous cell carcinoma (OSCC) is a malignant tumor originating from the oral mucosa, predominantly affecting the tongue, buccal mucosa, and floor of the mouth. This review summarizes recent progress in identifying novel biomarkers for OSCC, with particular focus on components of the tumor microenvironment (TME) involved in immune evasion, matrix remodeling, and angiogenesis. In addition, epigenetic alterations— including DNA methylation, histone modifications, and dysregulated non-coding RNAs—are investigated for their roles in OSCC progression. The role of extracellular vesicles (EVs) is further demonstrated, as they serve as critical mediators of intercellular communication linking the TME and epigenetic regulatory networks. Moreover, High-throughput technologies, such as single-cell sequencing and mass spectrometry, provide powerful tools to uncover the molecular mechanisms underlying these processes.
{"title":"Molecular markers in oral squamous cell carcinoma: Insights into the tumor microenvironment, epigenetic regulation, and intercellular communications","authors":"Xiaoran Zhen , Dongyan Zhang , Dongbao Li , Bo Fu , Keyi Li","doi":"10.1016/j.bbcan.2025.189516","DOIUrl":"10.1016/j.bbcan.2025.189516","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC) is a malignant tumor originating from the oral mucosa, predominantly affecting the tongue, buccal mucosa, and floor of the mouth. This review summarizes recent progress in identifying novel biomarkers for OSCC, with particular focus on components of the tumor microenvironment (TME) involved in immune evasion, matrix remodeling, and angiogenesis. In addition, epigenetic alterations— including DNA methylation, histone modifications, and dysregulated non-coding RNAs—are investigated for their roles in OSCC progression. The role of extracellular vesicles (EVs) is further demonstrated, as they serve as critical mediators of intercellular communication linking the TME and epigenetic regulatory networks. Moreover, High-throughput technologies, such as single-cell sequencing and mass spectrometry, provide powerful tools to uncover the molecular mechanisms underlying these processes.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189516"},"PeriodicalIF":9.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784087","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 : 2025-12-11DOI: 10.1016/j.bbcan.2025.189514
Abdul Momin Muhammad Wisal , Raheleh Farahzadi , Gayathri Rajaraman , Ezzatollah Fathi
Cancer remains one of the leading causes of mortality worldwide. Among these, hematologic malignancies originating in the bone marrow present unique challenges for in vivo modeling due to their complex pathophysiology and dynamic microenvironment. Over the years, numerous approaches have been developed better to understand cancer initiation, progression, and therapeutic resistance. The advent of three-dimensional (3D) organoid culture has accelerated progress in molecular and cellular oncology by providing physiologically relevant models that recapitulate key aspects of human tissues. Derived from pluripotent stem cells or patient-derived samples, organoids replicate essential structural and functional features of native tissues, thereby enabling detailed investigations of disease progression, immune interactions, and treatment responses. This review outlines the historical development and emerging applications of organoid systems in cancer research. Furthermore, introduce hematologic organoids and how bone marrow (BM), lymph nodes (LNs), thymus, and spleen organoids can replicate the hematologic malignancies for personalized therapies and research studies. Additionally, we highlight the influences of key signaling pathways—including Notch, TGF-β, JAK/STAT, and Hedgehog—in regulating hematopoiesis and leukemogenesis within hematologic organoid platforms. Moreover, advances in co-culture systems that integrate tumor cells with stromal and immune components have provided powerful tools for modeling the hematology tumor microenvironment by enhancing preclinical drug testing and introducing personalized therapeutic strategies. As the field advances, the integration of organoid technology with bioengineering approaches and multi-omics platforms is expected to revolutionize translational research and accelerate the development of novel therapies for hematologic cancers.
{"title":"Organoids as a new approach in advancing cancer therapies for hematologic malignancies","authors":"Abdul Momin Muhammad Wisal , Raheleh Farahzadi , Gayathri Rajaraman , Ezzatollah Fathi","doi":"10.1016/j.bbcan.2025.189514","DOIUrl":"10.1016/j.bbcan.2025.189514","url":null,"abstract":"<div><div>Cancer remains one of the leading causes of mortality worldwide. Among these, hematologic malignancies originating in the bone marrow present unique challenges for <em>in vivo</em> modeling due to their complex pathophysiology and dynamic microenvironment. Over the years, numerous approaches have been developed better to understand cancer initiation, progression, and therapeutic resistance. The advent of three-dimensional (3D) organoid culture has accelerated progress in molecular and cellular oncology by providing physiologically relevant models that recapitulate key aspects of human tissues. Derived from pluripotent stem cells or patient-derived samples, organoids replicate essential structural and functional features of native tissues, thereby enabling detailed investigations of disease progression, immune interactions, and treatment responses. This review outlines the historical development and emerging applications of organoid systems in cancer research. Furthermore, introduce hematologic organoids and how bone marrow (BM), lymph nodes (LNs), thymus, and spleen organoids can replicate the hematologic malignancies for personalized therapies and research studies. Additionally, we highlight the influences of key signaling pathways—including Notch, TGF-β, JAK/STAT, and Hedgehog—in regulating hematopoiesis and leukemogenesis within hematologic organoid platforms. Moreover, advances in co-culture systems that integrate tumor cells with stromal and immune components have provided powerful tools for modeling the hematology tumor microenvironment by enhancing preclinical drug testing and introducing personalized therapeutic strategies. As the field advances, the integration of organoid technology with bioengineering approaches and multi-omics platforms is expected to revolutionize translational research and accelerate the development of novel therapies for hematologic cancers.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189514"},"PeriodicalIF":9.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752423","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 : 2025-12-09DOI: 10.1016/j.bbcan.2025.189508
Graziana Spoto , Massimo Libra , Luca Falzone
Raf kinase inhibitor protein (RKIP), also known as Phosphatidyl Ethanolamine Binding Protein (PEBP1), is a pivotal modulator of multiple intracellular signaling cascades involved in tumorigenesis, progression, metastasis, and cancer therapy resistance. In recent years, increasing evidence has highlighted the regulatory role of non-coding RNAs, particularly microRNAs (miRNAs), in modulating RKIP expression and activity across various types of cancer. This review aims to comprehensively summarize current knowledge on the post-transcriptional regulation of RKIP by miRNAs, elucidating their impact on tumor biology.
For this purpose, a systematic analysis of published experimental studies was conducted, focusing on both solid and hematological malignancies. The review discusses how miRNAs, such as miR-23a, miR-27a, miR-224, miR-181a, and others, directly or indirectly suppress RKIP, contributing to enhanced proliferation, invasion, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) traits, and radioresistance. Additionally, long non-coding RNAs (lncRNAs) like XIST and PEBP1P2 were identified as factors able to modulate RKIP suppression by acting as molecular sponges for miRNAs or stabilizing RKIP transcripts.
All the data presented in the manuscript are supported by diverse experimental approaches, including transcriptional analyses, functional in vitro assays (migration, invasion, apoptosis), gain- and loss-of-function experiments, luciferase reporter assays, and in vivo xenograft models, further validating the miRNA-RKIP axis involved in the progression of multiple tumors.
In conclusion, this review provides an integrated view of the complex post-transcriptional network governing RKIP regulation in cancer, underscoring the potential of targeting RKIP-associated non-coding RNA axes for innovative therapeutic strategies aimed at halting tumor progression and overcoming treatment resistance.
{"title":"Role of microRNAs in the regulation of RKIP and signaling pathways in cancer","authors":"Graziana Spoto , Massimo Libra , Luca Falzone","doi":"10.1016/j.bbcan.2025.189508","DOIUrl":"10.1016/j.bbcan.2025.189508","url":null,"abstract":"<div><div>Raf kinase inhibitor protein (RKIP), also known as Phosphatidyl Ethanolamine Binding Protein (PEBP1), is a pivotal modulator of multiple intracellular signaling cascades involved in tumorigenesis, progression, metastasis, and cancer therapy resistance. In recent years, increasing evidence has highlighted the regulatory role of non-coding RNAs, particularly microRNAs (miRNAs), in modulating RKIP expression and activity across various types of cancer. This review aims to comprehensively summarize current knowledge on the post-transcriptional regulation of RKIP by miRNAs, elucidating their impact on tumor biology.</div><div>For this purpose, a systematic analysis of published experimental studies was conducted, focusing on both solid and hematological malignancies. The review discusses how miRNAs, such as miR-23a, miR-27a, miR-224, miR-181a, and others, directly or indirectly suppress RKIP, contributing to enhanced proliferation, invasion, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) traits, and radioresistance. Additionally, long non-coding RNAs (lncRNAs) like XIST and PEBP1P2 were identified as factors able to modulate RKIP suppression by acting as molecular sponges for miRNAs or stabilizing RKIP transcripts.</div><div>All the data presented in the manuscript are supported by diverse experimental approaches, including transcriptional analyses, functional in vitro assays (migration, invasion, apoptosis), gain- and loss-of-function experiments, luciferase reporter assays, and in vivo xenograft models, further validating the miRNA-RKIP axis involved in the progression of multiple tumors.</div><div>In conclusion, this review provides an integrated view of the complex post-transcriptional network governing RKIP regulation in cancer, underscoring the potential of targeting RKIP-associated non-coding RNA axes for innovative therapeutic strategies aimed at halting tumor progression and overcoming treatment resistance.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1881 1","pages":"Article 189508"},"PeriodicalIF":9.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746233","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 : 2025-12-08DOI: 10.1016/j.bbcan.2025.189513
Zihan Li , Xichen Dong , Jian Liu, Tao Wen
Colorectal cancer (CRC) exhibits extensive alterations in glycosylation, characterized by remodeling of glycan chain structures, aberrant terminal modifications, and dysregulated glycosyltransferase activity. These alterations are intimately associated with malignant phenotypes, such as tumor invasion, migration and proliferation, and contribute to shaping an immunosuppressive tumor microenvironment (TME). In this review, we first delineate major glycosylation types implicated in CRC, including O-GalNAc glycosylation, O-GlcNAcylation, N-glycosylation, sialylation, glycosphingolipid, glycosaminoglycan, and other special antigens, and summarize the key enzymatic machinery governing their biosynthesis. We further explore how glycosylation reprogramming drives oncogenic signaling and cellular plasticity. Importantly, we highlight recent advances in CRC-specific glycosylation-based diagnostic, prognostic, and therapeutic strategies. By summarizing current mechanistic and translational insights, this review aims to establish a conceptual framework for elucidating CRC-specific glycosylation alterations and evaluating their clinical translational potential, with the goal of improving early diagnosis, prognostic assessment, and targeted therapeutic strategies.
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