Biochimica et biophysica acta. Reviews on cancer最新文献

{"title":"Dual faces of angiogenesis: Mechanisms and therapeutic applications","authors":"Reza Izadpanah ,&nbsp;Amin Izadpanah ,&nbsp;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_vβ₃ (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}

{"title":"Advances in artificial intelligence for spatial transcriptomics in cancer: Special focus on Yin Yang 1 (YY1) and Raf kinase inhibitor protein (RKIP)","authors":"Lekhya Dommalapati ,&nbsp;Rachael Guenter ,&nbsp;Yuvasri Golivi ,&nbsp;Swapna Priya Ganji ,&nbsp;Tatekalva Sandhya ,&nbsp;Ganji Purnachandra Nagaraju ,&nbsp;Madhu Sudhana Saddala","doi":"10.1016/j.bbcan.2025.189456","DOIUrl":"10.1016/j.bbcan.2025.189456","url":null,"abstract":"<div><div>Spatial transcriptomics (ST) plays a pivotal role in cancer research, offering a unique perspective on gene expression within the cancer microenvironment, further revolutionizing our current understanding of the subject. From addressing the limitations of traditional bulk RNA sequencing by preserving spatial context, this review discusses the importance of integrating machine learning (ML), artificial intelligence (AI), and statistical methods for interpreting ST data within oncology. Herein, we use examples from studies involving Raf kinase inhibitor protein (RKIP) and Ying Yang 1 (YY1) to illustrate applications for some of the ST techniques discussed. We explore how applying supervised learning techniques, such as Support Vector Machines (SVMs) and Random Forests (RFs), can significantly help further cancer classification and prediction of clinical outcomes and advance personalized medicine. Additionally, exploring unsupervised learning approaches like clustering and dimensionality reduction methods (PCA, t-SNE, UMAP) allows us to see hidden structures in ST data that may be overlooked. This review discusses recent tools and techniques that have been introduced within the last few years, underlining the transformation brought into ST by ML, AI, and statistical methods that provide new insight into oncogenic drivers such as YY1 and RKIP, cancer heterogeneity, and avenues for personalized medicine approaches in cancer treatment.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189456"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139463","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}

{"title":"Targeting sex hormone signaling: A promising therapeutic alternative for glioblastoma","authors":"Juan Carlos Quintero,&nbsp;Omar Rafael Alemán,&nbsp;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}

{"title":"Tumor-associated high endothelial venules as therapeutic modulation targets in cancer immunotherapy","authors":"Jun-Ye Zhang ,&nbsp;Zhi-Yan Piao ,&nbsp;Guang-Liang Su ,&nbsp;Meng-Jie Zhang ,&nbsp;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}

{"title":"Role of macrophage PKM2 in inflammation and tumor progression and its targeted therapy","authors":"Yafei Li ,&nbsp;Lingao Zhu ,&nbsp;Lu Liu,&nbsp;Bo Li","doi":"10.1016/j.bbcan.2025.189478","DOIUrl":"10.1016/j.bbcan.2025.189478","url":null,"abstract":"<div><div>Macrophages play a dual role of promoting or inhibiting in inflammation and tumor progression, highly dependent on the dynamic changes of M1/M2 polarization. In inflammation, M1/M2 polarization balance determines the outbreak of inflammation or tissue repair. In the tumor microenvironment, M1 tumor-associated macrophages (TAMs) exert both anti-tumor and pro-tumor effects, while M2 TAMs promote tumor progression. PKM2 regulates the M1/M2 polarization and cytokine secretion of macrophages through the pyruvate kinase activity of tetramers as well as the protein kinase activity and transcriptional co-activator function of dimers. This review summarizes the role and molecular mechanism of macrophage PKM2 in inflammation and tumor progression, highlighting its potential as a therapeutic target in inflammatory diseases and cancers. Macrophage PKM2 plays a promoting role in inflammation and tumor progression due to its dual regulatory characteristics of metabolism and immunity. It can not only meet the energy demands of macrophages through glycolytic metabolism, but also affect the immune response through enzyme activity-dependent and non-dependent mechanisms. The non-enzyme activity-dependent mechanism by which PKM2 regulates immune responses serves as a bridge connecting cellular metabolism and immune responses. The unresolved issues include the functional heterogeneity of macrophage PKM2 across different macrophage subtypes, its specific roles in lipid and amino acid metabolism, its contribution to tumor microenvironmental metabolic reprogramming, and PKM2-mediated interactions of macrophages with other cells.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189478"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310194","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}

{"title":"Employing bacteriophages to combat cancer","authors":"Alicja Węgrzyn ,&nbsp;Sylwia Bloch ,&nbsp;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}

{"title":"AI-powered vaccine breakthroughs: Targeting pancreatic cancer with neoantigens and combination therapies","authors":"Jiaxin Zhang ,&nbsp;Lin Xiao ,&nbsp;Yueshui Zhang ,&nbsp;Gang Jin ,&nbsp;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}

{"title":"Unraveling the role of mitochondrial dynamics in cancer stem cells: Molecular basis and therapeutic implications","authors":"Gaia Giannitti,&nbsp;Sara Marchesi,&nbsp;Riccardo Garavaglia,&nbsp;Ivan Preosto,&nbsp;Fabrizio Fontana","doi":"10.1016/j.bbcan.2025.189450","DOIUrl":"10.1016/j.bbcan.2025.189450","url":null,"abstract":"<div><div>Many tumors consist of heterogeneous cell populations derived from a minority of cancer stem cells (CSCs), which possess distinct metabolic profiles that contribute to resistance against conventional anticancer therapy and increase the risk of tumor relapse. These unique CSC phenotypes are largely supported by altered mitochondrial function and turnover, regulated through continuous cycles of mitochondrial biogenesis, fission, fusion, and mitophagy. Consequently, understanding mitochondrial regulatory mechanisms in CSCs could reveal novel targets for cancer therapy. This article explores how mitochondrial dynamics contribute to CSC metabolic adaptation and drug resistance, alongside recent advances in the development of mitochondria-targeted drugs and their therapeutic usage.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189450"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056341","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}

{"title":"The mechanical landscape of cancer: Exploring mechanical characteristics-based therapeutic approaches","authors":"Hongdan Chen ,&nbsp;Yinde Huang ,&nbsp;Supeng Yin ,&nbsp;Chong Li ,&nbsp;Fan Zhang","doi":"10.1016/j.bbcan.2025.189463","DOIUrl":"10.1016/j.bbcan.2025.189463","url":null,"abstract":"<div><div>Tumor mechanical alterations have emerged as a critical but underexplored marker of cancer. Cells within the tumor microenvironment (TME) are constantly exposed to matrix remodeling, aberrant shear stress, cytoskeletal tension, and tumor thrombi, all of which modulate tumor progression, therapy resistance, and stromal remodeling. This review summarizes recent advances in understanding how mechanical cues regulate tumor behavior through mechanotransduction pathways, and evaluates therapeutic strategies targeting extracellular matrix (ECM) stiffness, cytoskeletal contractility, ion channels, and physical interventions. While these approaches demonstrate translational promise, most studies remain descriptive, and major challenges, including off-target effects, limited drug penetration, and biomarker validation, continue to impede clinical application. We highlight the emerging concept of “tumor mechanomics”, which integrates biomechanical fingerprints with molecular and clinical data, offering a framework for developing predictive biomarkers and guiding precision oncology.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 6","pages":"Article 189463"},"PeriodicalIF":9.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187980","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}

{"title":"Immune archetypes TIME classification system for nasopharyngeal carcinoma: A new direction for precision immunotherapy","authors":"Fei Lu ,&nbsp;Xueqi Bai ,&nbsp;Zihan Lv ,&nbsp;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}