BRCA1 is widely recognized as a guardian of the genome due to its established roles in DNA damage repair and cell cycle regulation. Nevertheless, these functions alone do not fully account for the tissue-specific defects and tumor phenotypes associated with pathogenic BRCA1 variants.
Accumulating evidence indicates that BRCA1 is also essential for RNA processing. In addition to modulating the activity of RNA polymerases, shaping chromatin architecture, and interacting with key transcription factors, BRCA1 influences splicing-factor function and helps prevent and resolve R-loop accumulation, thereby regulating both transcription and genomic integrity.
In response to DNA damage, BRCA1 participates in a complex containing components of the mRNA splicing machinery, thus altering the splicing pattern of several DNA damage response (DDR) genes. Moreover, BRCA1 orchestrates the transcription of molecules specific to epithelial and luminal breast cells, such as hormone receptors and growth factors, and factors involved in immune and inflammatory pathways.
This review discusses and organizes the growing body of evidence demonstrating how BRCA1 integrates transcriptional control and RNA processing and, in doing so, preserves a normal epithelial phenotype.
{"title":"Beyond repair: Expanding roles of BRCA1 in RNA processing and cancer","authors":"Mahsa Rastegar Moghaddam Poorbagher, Manuela Santarosa","doi":"10.1016/j.bbcan.2025.189499","DOIUrl":"10.1016/j.bbcan.2025.189499","url":null,"abstract":"<div><div>BRCA1 is widely recognized as a guardian of the genome due to its established roles in DNA damage repair and cell cycle regulation. Nevertheless, these functions alone do not fully account for the tissue-specific defects and tumor phenotypes associated with pathogenic BRCA1 variants.</div><div>Accumulating evidence indicates that BRCA1 is also essential for RNA processing. In addition to modulating the activity of RNA polymerases, shaping chromatin architecture, and interacting with key transcription factors, BRCA1 influences splicing-factor function and helps prevent and resolve R-loop accumulation, thereby regulating both transcription and genomic integrity.</div><div>In response to DNA damage, BRCA1 participates in a complex containing components of the mRNA splicing machinery, thus altering the splicing pattern of several DNA damage response (DDR) genes. Moreover, BRCA1 orchestrates the transcription of molecules specific to epithelial and luminal breast cells, such as hormone receptors and growth factors, and factors involved in immune and inflammatory pathways.</div><div>This review discusses and organizes the growing body of evidence demonstrating how BRCA1 integrates transcriptional control and RNA processing and, in doing so, preserves a normal epithelial phenotype.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189499"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575159","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189491
Woo Hyun Park
Mitochondria, far from being mere cellular powerhouses, act as central command hubs dictating cell fate by integrating metabolic cues with life-or-death decisions. In cancer, these organelles undergo profound functional and structural reprogramming to support relentless proliferation, survival, and adaptation to stress. This metabolic plasticity, however, creates unique vulnerabilities exploitable for therapeutic gain. This comprehensive review synthesizes recent insights into the multifaceted roles of mitochondria in cancer, focusing on how inhibiting their core functions can trigger diverse cell death pathways and modulate the tumor microenvironment. This paper delves into the central role of mitochondria in orchestrating various forms of regulated cell death (RCD), including apoptosis, ferroptosis, necroptosis, and the newly defined cuproptosis. A primary focus is placed on the dual nature of mitochondrial reactive oxygen species (ROS), which can promote tumorigenesis but can also be pharmacologically elevated to catastrophic levels, triggering oxidative stress-induced demise. This review systematically categorizes and discusses a burgeoning pharmacopeia of mitochondrial inhibitors—targeting the electron transport chain (ETC), metabolic enzymes like glutaminase, protein homeostasis, and ion channels—and analyzes their mechanisms of action, preclinical evidence, and clinical translation status. Furthermore, this paper examines how these agents can overcome chemoresistance and synergize with existing treatments, including the exciting interface with immunotherapy, where mitochondrial fitness is paramount for robust anti-tumor T-cell responses and the induction of immunogenic cell death (ICD). By dissecting the complex interplay between mitochondrial inhibition, metabolic disruption, oxidative stress, and cell death, this review highlights the immense promise of mitochondria-targeted therapies and charts the course for future innovations in oncology.
{"title":"The mitochondrial nexus: Targeting metabolic vulnerabilities, oxidative stress, and immunomodulation to induce cancer cell death","authors":"Woo Hyun Park","doi":"10.1016/j.bbcan.2025.189491","DOIUrl":"10.1016/j.bbcan.2025.189491","url":null,"abstract":"<div><div>Mitochondria, far from being mere cellular powerhouses, act as central command hubs dictating cell fate by integrating metabolic cues with life-or-death decisions. In cancer, these organelles undergo profound functional and structural reprogramming to support relentless proliferation, survival, and adaptation to stress. This metabolic plasticity, however, creates unique vulnerabilities exploitable for therapeutic gain. This comprehensive review synthesizes recent insights into the multifaceted roles of mitochondria in cancer, focusing on how inhibiting their core functions can trigger diverse cell death pathways and modulate the tumor microenvironment. This paper delves into the central role of mitochondria in orchestrating various forms of regulated cell death (RCD), including apoptosis, ferroptosis, necroptosis, and the newly defined cuproptosis. A primary focus is placed on the dual nature of mitochondrial reactive oxygen species (ROS), which can promote tumorigenesis but can also be pharmacologically elevated to catastrophic levels, triggering oxidative stress-induced demise. This review systematically categorizes and discusses a burgeoning pharmacopeia of mitochondrial inhibitors—targeting the electron transport chain (ETC), metabolic enzymes like glutaminase, protein homeostasis, and ion channels—and analyzes their mechanisms of action, preclinical evidence, and clinical translation status. Furthermore, this paper examines how these agents can overcome chemoresistance and synergize with existing treatments, including the exciting interface with immunotherapy, where mitochondrial fitness is paramount for robust anti-tumor T-cell responses and the induction of immunogenic cell death (ICD). By dissecting the complex interplay between mitochondrial inhibition, metabolic disruption, oxidative stress, and cell death, this review highlights the immense promise of mitochondria-targeted therapies and charts the course for future innovations in oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189491"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433375","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189486
Juan Carlos Quintero, Omar Rafael Alemán, Ignacio Camacho-Arroyo
Glioblastoma is the most common and malignant primary brain tumor of the central nervous system, with conventional therapy yielding very poor results in overall patient survival and quality of life. The low life expectancy at diagnosis of just 15 months, highlights the need for novel therapeutic alternatives. Glioblastoma has a higher incidence in men than in women, suggesting a critical role of sex hormone signaling in tumor maintenance and progression. There is now ample evidence that sex hormones impact glioblastoma malignancy. Testosterone, through the androgen receptor, promotes proliferation, migration, and invasion of tumor cells. Interestingly, estradiol and progesterone show both pro- and anti-tumor effects, depending on the dose and the specific receptors expressed in the cells. Sex hormones regulate gene activity by binding to intracellular receptors, which act as ligand-activated transcription factors. Additionally, the presence of membrane receptors for estrogens and progesterone can promote rapid cellular responses, activating signaling pathways such as PI3K/AKT and MAPK in tumor cells. Thus, the regulation of sex hormone activity and receptor function can directly affect tumor progression and survival. This article analyzes the impact of sex hormone signaling on the malignancy of glioblastomas.
{"title":"Targeting sex hormone signaling: A promising therapeutic alternative for glioblastoma","authors":"Juan Carlos Quintero, Omar Rafael Alemán, Ignacio Camacho-Arroyo","doi":"10.1016/j.bbcan.2025.189486","DOIUrl":"10.1016/j.bbcan.2025.189486","url":null,"abstract":"<div><div>Glioblastoma is the most common and malignant primary brain tumor of the central nervous system, with conventional therapy yielding very poor results in overall patient survival and quality of life. The low life expectancy at diagnosis of just 15 months, highlights the need for novel therapeutic alternatives. Glioblastoma has a higher incidence in men than in women, suggesting a critical role of sex hormone signaling in tumor maintenance and progression. There is now ample evidence that sex hormones impact glioblastoma malignancy. Testosterone, through the androgen receptor, promotes proliferation, migration, and invasion of tumor cells. Interestingly, estradiol and progesterone show both pro- and anti-tumor effects, depending on the dose and the specific receptors expressed in the cells. Sex hormones regulate gene activity by binding to intracellular receptors, which act as ligand-activated transcription factors. Additionally, the presence of membrane receptors for estrogens and progesterone can promote rapid cellular responses, activating signaling pathways such as PI3K/AKT and MAPK in tumor cells. Thus, the regulation of sex hormone activity and receptor function can directly affect tumor progression and survival. This article analyzes the impact of sex hormone signaling on the malignancy of glioblastomas.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189486"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412486","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189494
Reza Izadpanah , Amin Izadpanah , Eckhard U. Alt
Angiogenesis is a highly coordinated process essential for development, tissue homeostasis, and repair. In physiologic settings, endothelial cells remain quiescent until transient hypoxia- or injury-induced surges of VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), and other pro-angiogenic cues activate receptor tyrosine kinases, triggering MAPK (mitogen-activated protein kinase) and PI3K–AKT (phosphoinositide 3-kinase–AKT) cascades that drive sprouting, proliferation, migration, and vessel stabilization via pericyte recruitment and balanced Ang (angiopoietin)–Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2) signaling. In non-malignant pathologies, targeted pro-angiogenic therapies harness these mechanisms to restore perfusion in ischemic heart disease, chronic wounds, and neurovascular degeneration. In contrast, tumor-driven “malignant” angiogenesis subverts the same core pathways in both hypoxia-dependent and -independent manners. Oncogenic RAS (rat sarcoma)–RAF (rapidly accelerated fibrosarcoma)–MEK (MAPK/ERK kinase) and PI3K–AKT activity locks VEGFR2 (vascular endothelial growth factor receptor 2) Tyr1175 in a phosphorylated state, fueling unchecked endothelial proliferation and survival. Overexpression of integrin αvβ3 (alpha-v beta-3) and NRP2 (neuropilin 2) amplifies FAK (focal adhesion kinase)-Src-mediated invasion, while glycocalyx shedding and uneven pericyte coverage produce leaky vasculature. Transient vessel normalization upon VEGF blockade is followed by adaptive resistance via HIF (hypoxia-inducible factor)–driven upregulation of FGF2, Ang-2 (angiopoietin-2), and HGF (hepatocyte growth factor)/c-Met pathways, necessitating complex combination regimens. Rationally distinguishing when to inhibit versus augment angiogenesis is therefore clinically decisive, because cancers demand vascular suppression/normalization whereas ischemic and degenerative disorders benefit from controlled pro-angiogenic repair. We compared malignant and non-malignant angiogenesis at the molecular and clinical levels, critically appraising therapies, from VEGF antibodies and multitarget TKIs (tyrosine kinase inhibitors) to pro-angiogenic growth factors and drug-delivery platforms, and their respective biomarkers (Ang-2, soluble VEGFR2, VEGF isoform ratios). By explicitly linking pathway mechanics to therapeutic choice, dosing, and biomarker-guided selection, this review provides a comprehensive roadmap for tailoring angiogenesis-targeted interventions, either to restrain pathological neovascularization in cancer or to promote reparative vessel growth in ischemic and degenerative disease.
{"title":"Dual faces of angiogenesis: Mechanisms and therapeutic applications","authors":"Reza Izadpanah , Amin Izadpanah , Eckhard U. Alt","doi":"10.1016/j.bbcan.2025.189494","DOIUrl":"10.1016/j.bbcan.2025.189494","url":null,"abstract":"<div><div>Angiogenesis is a highly coordinated process essential for development, tissue homeostasis, and repair. In physiologic settings, endothelial cells remain quiescent until transient hypoxia- or injury-induced surges of VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), and other pro-angiogenic cues activate receptor tyrosine kinases, triggering MAPK (mitogen-activated protein kinase) and PI3K–AKT (phosphoinositide 3-kinase–AKT) cascades that drive sprouting, proliferation, migration, and vessel stabilization via pericyte recruitment and balanced Ang (angiopoietin)–Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2) signaling. In non-malignant pathologies, targeted pro-angiogenic therapies harness these mechanisms to restore perfusion in ischemic heart disease, chronic wounds, and neurovascular degeneration. In contrast, tumor-driven “malignant” angiogenesis subverts the same core pathways in both hypoxia-dependent and -independent manners. Oncogenic RAS (rat sarcoma)–RAF (rapidly accelerated fibrosarcoma)–MEK (MAPK/ERK kinase) and PI3K–AKT activity locks VEGFR2 (vascular endothelial growth factor receptor 2) Tyr1175 in a phosphorylated state, fueling unchecked endothelial proliferation and survival. Overexpression of integrin α<sub>v</sub>β<sub>3</sub> (alpha-v beta-3) and NRP2 (neuropilin 2) amplifies FAK (focal adhesion kinase)-Src-mediated invasion, while glycocalyx shedding and uneven pericyte coverage produce leaky vasculature. Transient vessel normalization upon VEGF blockade is followed by adaptive resistance via HIF (hypoxia-inducible factor)–driven upregulation of FGF2, Ang-2 (angiopoietin-2), and HGF (hepatocyte growth factor)/c-Met pathways, necessitating complex combination regimens. Rationally distinguishing when to inhibit versus augment angiogenesis is therefore clinically decisive, because cancers demand vascular suppression/normalization whereas ischemic and degenerative disorders benefit from controlled pro-angiogenic repair. We compared malignant and non-malignant angiogenesis at the molecular and clinical levels, critically appraising therapies, from VEGF antibodies and multitarget TKIs (tyrosine kinase inhibitors) to pro-angiogenic growth factors and drug-delivery platforms, and their respective biomarkers (Ang-2, soluble VEGFR2, VEGF isoform ratios). By explicitly linking pathway mechanics to therapeutic choice, dosing, and biomarker-guided selection, this review provides a comprehensive roadmap for tailoring angiogenesis-targeted interventions, either to restrain pathological neovascularization in cancer or to promote reparative vessel growth in ischemic and degenerative disease.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189494"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515248","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189500
Jun-Ye Zhang , Zhi-Yan Piao , Guang-Liang Su , Meng-Jie Zhang , Zhi-Jun Sun
Immunotherapy has shown remarkable efficacy in improving the prognosis and survival rates of cancer patients, yet the overall response rate remains relatively low. The discovery of high endothelial venules (HEVs) and tertiary lymphoid structures (TLSs) has brought new hope to antitumor immunity. HEVs, as specialized vascular structures, facilitate lymphocyte infiltration and enhance tumor immune responses, while TLSs provide an organized immune microenvironment that further supports antitumor immunity. Current studies often emphasize the immunoregulatory roles of HEVs or TLSs from relatively independent perspectives, overlooking the fact that the two constitute a temporospatially interactive and unified system. This review systematically explores the interdependence and interactions between tumor-associated high endothelial venules (TA-HEVs) and TLSs in terms of their development, organization, and function. From an integrative perspective, it highlights current pharmacological strategies aimed at inducing intratumoral HEVs and TLSs to enhance the efficacy of immunotherapy. Finally, the review discusses future perspectives on the potential molecular mechanisms underlying HEV formation, methodologies for HEV detection, and the development of precision-targeted therapies to modulate HEV/TLS formation.
{"title":"Tumor-associated high endothelial venules as therapeutic modulation targets in cancer immunotherapy","authors":"Jun-Ye Zhang , Zhi-Yan Piao , Guang-Liang Su , Meng-Jie Zhang , Zhi-Jun Sun","doi":"10.1016/j.bbcan.2025.189500","DOIUrl":"10.1016/j.bbcan.2025.189500","url":null,"abstract":"<div><div>Immunotherapy has shown remarkable efficacy in improving the prognosis and survival rates of cancer patients, yet the overall response rate remains relatively low. The discovery of high endothelial venules (HEVs) and tertiary lymphoid structures (TLSs) has brought new hope to antitumor immunity. HEVs, as specialized vascular structures, facilitate lymphocyte infiltration and enhance tumor immune responses, while TLSs provide an organized immune microenvironment that further supports antitumor immunity. Current studies often emphasize the immunoregulatory roles of HEVs or TLSs from relatively independent perspectives, overlooking the fact that the two constitute a temporospatially interactive and unified system. This review systematically explores the interdependence and interactions between tumor-associated high endothelial venules (TA-HEVs) and TLSs in terms of their development, organization, and function. From an integrative perspective, it highlights current pharmacological strategies aimed at inducing intratumoral HEVs and TLSs to enhance the efficacy of immunotherapy. Finally, the review discusses future perspectives on the potential molecular mechanisms underlying HEV formation, methodologies for HEV detection, and the development of precision-targeted therapies to modulate HEV/TLS formation.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189500"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650353","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189484
Jiaxin Zhang , Lin Xiao , Yueshui Zhang , Gang Jin , Kailian Zheng
The five-year survival rate for Pancreatic Ductal Adenocarcinoma (PDAC) remains below 10 %, primarily due to the limited efficacy of conventional chemotherapy and immune checkpoint inhibitors against its triple-immune-sequestered, low-TMB tumor microenvironment(TME). This situation has been furter exacerbated by the stagnation of traditional vaccine development, driven by inefficient antigen screening and high tumor heterogeneity.
Artificial intelligence (AI) exhibits remarkable advantages in the design of pancreatic ductal adenocarcinoma (PDAC) vaccines. It can integrate multi – omics data to efficiently unearth cryptic neoantigens from low - tumor mutation burden (TMB) samples, significantly enhancing the screening efficiency. Through dynamic modeling, AI can rationally plan the timing of combined vaccine therapies, effectively reducing the degree of T - cell exhaustion. By leveraging the digital twin model, AI can remarkably improve the matching accuracy between antigens and human leukocyte antigen (HLA). Additionally, it can construct a monitoring system to provide early warnings of antigen loss risks, thus gaining adjustment time for clinical treatments.This review aims to accomplish three primary objectives: demonstrate AI's potential in breaking the therapeutic impasse to overcome manufacturing-related treatment delays for 25–30 % of patients; further delineates the logical progression of AI from concept to clinical application; thereby provides a translational framework to bridge the gap between research and patient benefit.
{"title":"AI-powered vaccine breakthroughs: Targeting pancreatic cancer with neoantigens and combination therapies","authors":"Jiaxin Zhang , Lin Xiao , Yueshui Zhang , Gang Jin , Kailian Zheng","doi":"10.1016/j.bbcan.2025.189484","DOIUrl":"10.1016/j.bbcan.2025.189484","url":null,"abstract":"<div><div>The five-year survival rate for Pancreatic Ductal Adenocarcinoma (PDAC) remains below 10 %, primarily due to the limited efficacy of conventional chemotherapy and immune checkpoint inhibitors against its triple-immune-sequestered, low-TMB tumor microenvironment(TME). This situation has been furter exacerbated by the stagnation of traditional vaccine development, driven by inefficient antigen screening and high tumor heterogeneity.</div><div>Artificial intelligence (AI) exhibits remarkable advantages in the design of pancreatic ductal adenocarcinoma (PDAC) vaccines. It can integrate multi – omics data to efficiently unearth cryptic neoantigens from low - tumor mutation burden (TMB) samples, significantly enhancing the screening efficiency. Through dynamic modeling, AI can rationally plan the timing of combined vaccine therapies, effectively reducing the degree of T - cell exhaustion. By leveraging the digital twin model, AI can remarkably improve the matching accuracy between antigens and human leukocyte antigen (HLA). Additionally, it can construct a monitoring system to provide early warnings of antigen loss risks, thus gaining adjustment time for clinical treatments.This review aims to accomplish three primary objectives: demonstrate AI's potential in breaking the therapeutic impasse to overcome manufacturing-related treatment delays for 25–30 % of patients; further delineates the logical progression of AI from concept to clinical application; thereby provides a translational framework to bridge the gap between research and patient benefit.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189484"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370547","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189485
Alicja Węgrzyn , Sylwia Bloch , Grzegorz Węgrzyn
Bacteriophages are viruses infecting bacterial cells; therefore, their application in cancer research may initially appear counterintuitive. Nevertheless, bacteriophages have been employed in the development of numerous advanced biotechnological tools, which has led to the emergence of multiple approaches utilizing them for improved cancer diagnostics and novel therapeutic strategies. Unlike other recently published reviews in this field, this paper does not emphasize technological principles or focus on specific cancer type. Instead, we provide a broad overview of innovative concepts and highlight recent advances in the use of bacteriophages in anti-cancer research. In particular, we discuss their roles in: (i) early cancer diagnosis and detection of tumorigenic mutations, (ii) elimination of bacteria that promote carcinogenesis and modulation of the microbiome influencing tumor growth, (iii) development of anti-cancer vaccines, (iv) modulation of cancer-related immune responses, (v) targeted delivery of anti-cancer drugs, and (vi) genetic modification of cancer cells through therapeutic DNA delivery.
{"title":"Employing bacteriophages to combat cancer","authors":"Alicja Węgrzyn , Sylwia Bloch , Grzegorz Węgrzyn","doi":"10.1016/j.bbcan.2025.189485","DOIUrl":"10.1016/j.bbcan.2025.189485","url":null,"abstract":"<div><div>Bacteriophages are viruses infecting bacterial cells; therefore, their application in cancer research may initially appear counterintuitive. Nevertheless, bacteriophages have been employed in the development of numerous advanced biotechnological tools, which has led to the emergence of multiple approaches utilizing them for improved cancer diagnostics and novel therapeutic strategies. Unlike other recently published reviews in this field, this paper does not emphasize technological principles or focus on specific cancer type. Instead, we provide a broad overview of innovative concepts and highlight recent advances in the use of bacteriophages in anti-cancer research. In particular, we discuss their roles in: (i) early cancer diagnosis and detection of tumorigenic mutations, (ii) elimination of bacteria that promote carcinogenesis and modulation of the microbiome influencing tumor growth, (iii) development of anti-cancer vaccines, (iv) modulation of cancer-related immune responses, (v) targeted delivery of anti-cancer drugs, and (vi) genetic modification of cancer cells through therapeutic DNA delivery.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189485"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412481","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189487
Fei Lu , Xueqi Bai , Zihan Lv , Wenling Zhang
In the complex tumor immune microenvironment (TIME), tumor cells are typically surrounded by host immune components that can either suppress or promote tumor progression. The stromal compartment usually responds to tumor cells through inflammatory processes, often reflecting a single immune state or class. This pattern is also observed in the tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC). However, recent advances in single-cell profiling have revealed that multiple distinct immune states can coexist around NPC tissues. In this review, we delineate and classify the immune “archetypes” of TMEs in NPC—defined as cellular assemblages and gene expression profiles that are characteristic and recurrent at the bulk tumor level. We further summarize studies suggesting that NPC TMEs can be broadly categorized into 11 major immune archetypes. Considering their potential evolutionary origins and functional roles, these archetypes appear to be associated with specific vulnerabilities within the TME, which may be exploited as therapeutic targets. Such insights may provide novel strategies for NPC treatment, thereby enhancing patient outcomes and improving prognosis.
{"title":"Immune archetypes TIME classification system for nasopharyngeal carcinoma: A new direction for precision immunotherapy","authors":"Fei Lu , Xueqi Bai , Zihan Lv , Wenling Zhang","doi":"10.1016/j.bbcan.2025.189487","DOIUrl":"10.1016/j.bbcan.2025.189487","url":null,"abstract":"<div><div>In the complex tumor immune microenvironment (TIME), tumor cells are typically surrounded by host immune components that can either suppress or promote tumor progression. The stromal compartment usually responds to tumor cells through inflammatory processes, often reflecting a single immune state or class. This pattern is also observed in the tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC). However, recent advances in single-cell profiling have revealed that multiple distinct immune states can coexist around NPC tissues. In this review, we delineate and classify the immune “archetypes” of TMEs in NPC—defined as cellular assemblages and gene expression profiles that are characteristic and recurrent at the bulk tumor level. We further summarize studies suggesting that NPC TMEs can be broadly categorized into 11 major immune archetypes. Considering their potential evolutionary origins and functional roles, these archetypes appear to be associated with specific vulnerabilities within the TME, which may be exploited as therapeutic targets. Such insights may provide novel strategies for NPC treatment, thereby enhancing patient outcomes and improving prognosis.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189487"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412485","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189492
Wei Li , Tong Liu , Tianhua Wu , Ting Cai , Fen Wang , Minglin Zhang
Helicobacter pylori (H. pylori), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating H. pylori-induced gastric mucosal damage and carcinogenesis. We describe how H. pylori exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to H. pylori pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as H. pylori disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.
{"title":"Posttranslational modifications in Helicobacter pylori-associated gastric pathogenesis: Bridging inflammation and carcinogenesis","authors":"Wei Li , Tong Liu , Tianhua Wu , Ting Cai , Fen Wang , Minglin Zhang","doi":"10.1016/j.bbcan.2025.189492","DOIUrl":"10.1016/j.bbcan.2025.189492","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating <em>H. pylori</em>-induced gastric mucosal damage and carcinogenesis. We describe how <em>H. pylori</em> exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to <em>H. pylori</em> pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as <em>H. pylori</em> disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189492"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477374","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 : 2025-11-01DOI: 10.1016/j.bbcan.2025.189496
Xiangyu Huang, Si Zhang, Jiale Li, She Chen
Despite advances in PD-1/PD-L1 combination therapies, clinical benefits remain limited and toxicity is significant. Galectins, a family of β-galactoside-binding lectins, have emerged as mechanistically distinct, multimodal targets with the potential to address these limitations. By modulating glycan–protein networks in the tumor microenvironment, galectin inhibition alleviates T cell exclusion, immune exhaustion, immunosuppressive cell activation, and steric blockade of PD-(L)1 antibodies. Several galectin inhibitors (e.g., GR-MD-02, GB1211, LYT-200) are under clinical evaluation. Early trials showing encouraging efficacy-toxicity profiles and some combinations received FDA Fast Track designations. This review summarizes mechanistic and clinical advances and highlights their translational implications for galectin-targeted combination therapies.
{"title":"Rewiring PD-1/PD-L1 combination therapy via glyco-immune targeting of galectins: Toward clinical translation","authors":"Xiangyu Huang, Si Zhang, Jiale Li, She Chen","doi":"10.1016/j.bbcan.2025.189496","DOIUrl":"10.1016/j.bbcan.2025.189496","url":null,"abstract":"<div><div>Despite advances in PD-1/PD-L1 combination therapies, clinical benefits remain limited and toxicity is significant. Galectins, a family of β-galactoside-binding lectins, have emerged as mechanistically distinct, multimodal targets with the potential to address these limitations. By modulating glycan–protein networks in the tumor microenvironment, galectin inhibition alleviates T cell exclusion, immune exhaustion, immunosuppressive cell activation, and steric blockade of PD-(L)1 antibodies. Several galectin inhibitors (e.g., GR-MD-02, GB1211, LYT-200) are under clinical evaluation. Early trials showing encouraging efficacy-toxicity profiles and some combinations received FDA Fast Track designations. This review summarizes mechanistic and clinical advances and highlights their translational implications for galectin-targeted combination therapies.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189496"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516608","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}
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