Seminars in cancer biology最新文献

{"title":"Genomic instability, DNA damage response and telomere homeostasis in pancreatic cancer","authors":"Saba Selvi ,&nbsp;Carmen Macías Real ,&nbsp;Manuel Gentiluomo ,&nbsp;Katerina Balounova ,&nbsp;Klara Vokacova ,&nbsp;Andrea Cumova ,&nbsp;Beatrice Mohlenikova-Duchonova ,&nbsp;Cosmeri Rizzato ,&nbsp;Erika Halasova ,&nbsp;Ludmila Vodickova ,&nbsp;Bozena Smolkova ,&nbsp;Kari Hemminki ,&nbsp;Daniele Campa ,&nbsp;Pavel Vodicka","doi":"10.1016/j.semcancer.2025.05.005","DOIUrl":"10.1016/j.semcancer.2025.05.005","url":null,"abstract":"<div><div>Pancreatic cancer (PC) is becoming one of the most serious health problems at present, but its causes and risk factors are still unclear. One of the drivers in pancreatic carcinogenesis is altered genomic (DNA) integrity with subsequent genomic instability in cancer cells. The latter comprises a) DNA damage response and DNA repair mechanisms, b) DNA replication and mitosis, c) epigenetic regulation, and d) telomere maintenance. In our review we addressed the above aspects in relation to the most abundant and severe form of PC, pancreatic ductal adenocarcinoma (PDAC). In summary, the interactions between the DNA damage response, telomere homeostasis and mitotic regulation are not comprehensively understood at present, including the epigenetic factors entering the trait of genomic stability maintenance. In addition, the complexity of telomere homeostasis in relation to PDAC risk, prognosis and prediction also warrants further investigations.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 59-73"},"PeriodicalIF":12.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068054","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 potential application of stroma modulation in targeting tumor cells: focus on pancreatic cancer and breast cancer models.","authors":"Giuseppina Roscigno, Sacha Jacobs, Belen Toledo, Roberto Borea, Gianluca Russo, Francesco Pepe, Maria Jose Serrano, Viola Calabrò, Giancarlo Troncone, Roberto Giovannoni, Elisa Giovannetti, Umberto Malapelle","doi":"10.1016/j.semcancer.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.semcancer.2025.05.003","url":null,"abstract":"<p><p>The tumor microenvironment (TME) plays a crucial role in cancer development and spreading being considered as \"the dark side of the tumor\". Within this term tumor cells, immune components, supporting cells, extracellular matrix and a myriad of bioactive molecules that synergistically promote tumor development and therapeutic resistance, are included. Recent findings revealed the profound impacts of TME on cancer development, serving as physical support, critical mediator and biodynamic matrix in cancer evolution, immune modulation, and treatment outcomes. TME targeting strategies built on vasculature, immune checkpoints, and immuno-cell therapies, have paved the way for revolutionary clinical interventions. On this basis, the relevance of pre-clinical and clinical investigations has rapidly become fundamental for implementing novel therapeutical strategies breaking cell-cell and cell -mediators' interactions between TME components and tumor cells. This review summarizes the key players in the breast and pancreatic TME, elucidating the intricate interactions among cancer cells and their essential role for cancer progression and therapeutic resistance. Different tumors such breast and pancreatic cancer have both different and similar stroma features, that might affect therapeutic strategies. Therefore, this review aims to comprehensively evaluate recent findings for refining breast and pancreatic cancer therapies and improve patient prognoses by exploiting the TME's complexity in the next future.</p>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079915","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 exposome and pancreatic cancer, lifestyle and environmental risk factors for PDAC","authors":"Giulia Peduzzi ,&nbsp;Livia Archibugi ,&nbsp;Riccardo Farinella ,&nbsp;Ruggero Ponz de Leon Pisani ,&nbsp;Ludmila Vodickova ,&nbsp;Pavel Vodicka ,&nbsp;Bledar Kraja ,&nbsp;Juan Sainz ,&nbsp;David Bars-Cortina ,&nbsp;Neil Daniel ,&nbsp;Roberto Silvestri ,&nbsp;Pinar Uysal-Onganer ,&nbsp;Stefano Landi ,&nbsp;Joanna Dulińska-Litewka ,&nbsp;Annalisa Comandatore ,&nbsp;Daniele Campa ,&nbsp;David J. Hughes ,&nbsp;Cosmeri Rizzato","doi":"10.1016/j.semcancer.2025.05.004","DOIUrl":"10.1016/j.semcancer.2025.05.004","url":null,"abstract":"<div><div>Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma (PDAC), is a significant global health issue with high mortality rates. PDAC, though only 3 % of cancer diagnoses, causes 7 % of cancer deaths due to its severity and asymptomatic early stages. Risk factors include lifestyle choices, environmental exposures, and genetic predispositions. Conditions like new-onset type 2 diabetes and chronic pancreatitis also contribute significantly. Modifiable risk factors include smoking, alcohol consumption, non-alcoholic fatty pancreatic disease (NAFPD), and obesity. Smoking and heavy alcohol consumption increase PC risk, while NAFPD and obesity, particularly central adiposity, contribute through chronic inflammation and insulin resistance. Refined sugar and sugar-sweetened beverages (SSBs) are also linked to increased PC risk, especially among younger individuals. Hormonal treatments and medications like statins, aspirin, and metformin have mixed results on PC risk, with some showing protective effects. The gut microbiome influences PC through the gut-pancreas axis, with disruptions leading to inflammation and carcinogenesis. Exposure to toxic substances, including heavy metals and chemicals, is associated with increased PC risk. Glycome changes, such as abnormal glycosylation patterns, are significant in PDAC development and offer potential for early diagnosis. Interactions between environmental and genetic factors are crucial in PDAC susceptibility. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) linked to PDAC, but gene-environment interactions remain largely unexplored. Future research should focus on polygenic risk scores (PRS) and large-scale studies to better understand these interactions and their impact on PDAC risk.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 100-129"},"PeriodicalIF":12.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071476","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":"HDAC inhibitors: Cardiotoxicity and paradoxical cardioprotective effect in ischemia-reperfusion myocardiocyte injury","authors":"Kenneth K.W. To ,&nbsp;Seda S. Tolu ,&nbsp;Longling Wang ,&nbsp;Hang Zhang ,&nbsp;William C. Cho ,&nbsp;Susan E. Bates","doi":"10.1016/j.semcancer.2025.05.008","DOIUrl":"10.1016/j.semcancer.2025.05.008","url":null,"abstract":"<div><div>Histone deacetylase inhibitors (HDACIs) are epigenetic drugs that regulate the acetylation status of histones and non-histone proteins, thereby leading to chromatin remodeling and transcriptional regulation of key apoptotic and cell cycle regulatory genes. There are currently five HDACIs clinically approved by the major regulatory authorities for treating hematological cancers, primarily as monotherapy. While HDACIs have been particularly effective in T-cell lymphomas, their clinical efficacies have not yet extended to solid tumors. The development of HDACIs continues, including for the treatment of a non-malignant conditions, with givinostat recently approved by the US FDA. However, the early development of HDACIs was limited by concerns about cardiotoxicity including QT interval prolongation. Yet, paradoxically, the latest research suggests some cardioprotective effect of HDACIs in ischemic heart disease or heart failure. This review presents the latest update about the cardiotoxicity of the clinically approved HDACIs. The mechanisms leading to HDACI-induced cardiotoxic adverse events and clinical strategies for their management are discussed. We will also deliberate the potential repurposing use of HDACIs and their HDAC isoform selectivity for treating ischemia-reperfusion cardiac muscle injury, cardiac hypertrophy, and fibrosis.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 25-38"},"PeriodicalIF":12.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941863","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":"Metabolic reprogramming in cancer therapy-related cardiovascular toxicity: Mechanisms and intervention strategies","authors":"Cheng Zeng ,&nbsp;Ying Gao ,&nbsp;Bo Lan ,&nbsp;Jiani Wang ,&nbsp;Fei Ma","doi":"10.1016/j.semcancer.2025.05.009","DOIUrl":"10.1016/j.semcancer.2025.05.009","url":null,"abstract":"<div><div>Cancer therapy-related cardiovascular toxicity (CTR-CVT) poses a major challenge in managing cancer patients, contributing significantly to morbidity and mortality among survivors. CTR-CVT includes various cardiovascular issues, such as cardiomyopathy, myocardial ischemia, arrhythmias, and vascular dysfunction, which significantly impact patient prognosis and quality of life. Metabolic reprogramming, characterized by disruptions in glucose, lipid, and amino acid metabolism, represents a shared pathophysiological feature of cancer and cardiovascular diseases; however, the precise mechanisms underlying CTR-CVT remain inadequately understood. In recent years, strategies targeting metabolic pathways have shown promise in reducing cardiovascular risks while optimizing cancer treatment efficacy. This review systematically summarizes metabolic reprogramming characteristics in both cancer and cardiovascular diseases, analyzes how anticancer therapies induce cardiovascular toxicity through metabolic alterations, and explores emerging therapeutic strategies targeting metabolic dysregulation. By integrating current research advancements, this review aims to enhance the understanding of CTR-CVT and provide groundwork for the development of safer and more effective cancer approaches.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 39-58"},"PeriodicalIF":12.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947005","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":"Psychological stress on cancer progression and immunosenescence","authors":"Yinglin Huang ,&nbsp;Yuhong Zhan ,&nbsp;Yuhua Zhan","doi":"10.1016/j.semcancer.2025.05.007","DOIUrl":"10.1016/j.semcancer.2025.05.007","url":null,"abstract":"<div><div>Diagnosis and treatment of cancer constitute a deeply stressful experience that involves unique and common problems and generates uncertainty, fear and emotional distress. Furthermore, there are reciprocal interactions between psychological stress and cancer in the clinical settings. Therefore, it is crucial to understand the links of stress with cancer. A growing body of epidemiological and preclinical studies have suggested that stress affects cancer progression, and metastasis and treatment outcomes. Furthermore, stress elicits premature aging and deterioration of the immune system (known as immunosenescence), causing vulnerability to infections, autoimmune diseases, and cancers. In this review, we describe recent advances in how stress affects cancer progression through specific stress hormones and receptor systems as well as intracellular molecular processes, and discuss how stress-evoked neuroendocrine molecules regulate local and systemic immune responses in the tumor microenvironment. Furthermore, we review the molecular mechanisms of immunosenescence and evidence of psychological stress-evoked immunosenescence, highlighting the clinical value for available psychological and/or pharmacological interventions for psychological stress in patients with cancer. Based on existing evidence and emerging mechanistic insights, factors linked with psychological stress, immunosenescence and complications in cancer survivors need to be determined in future studies, and screening programs should be added to follow-up.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 85-99"},"PeriodicalIF":12.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043997","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":"Metabolic pathway analysis of tumors using stable isotopes","authors":"Qiufen Bi ,&nbsp;Junzhang Zhao ,&nbsp;Jun Nie ,&nbsp;Fang Huang","doi":"10.1016/j.semcancer.2025.05.002","DOIUrl":"10.1016/j.semcancer.2025.05.002","url":null,"abstract":"<div><div>Metabolic reprogramming is pivotal in malignant transformation and cancer progression. Tumor metabolism is shaped by a complex interplay of both intrinsic and extrinsic factors that are not yet fully elucidated. It is of great value to unravel the complex metabolic activity of tumors in patients. Metabolic flux analysis (MFA) is a versatile technique for investigating tumor metabolism <em>in vivo</em>, it has increasingly been applied to the assessment of metabolic activity in cancer in the past decade. Stable-isotope tracing have shown that human tumors use diverse nutrients to fuel central metabolic pathways, such as the tricarboxylic acid cycle and macromolecule synthesis. Precisely how tumors use different fuels, and the contribution of alternative metabolic pathways in tumor progression, remain areas of intensive investigation. In this review, we systematically summarize the evidence from <em>in vivo</em> stable- isotope tracing in tumors and describe the catabolic and anabolic processes involved in altered tumor metabolism. We also discuss current challenges and future perspectives for MFA of human cancers, which may provide new approaches in diagnosis and treatment of cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 9-24"},"PeriodicalIF":12.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941847","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":"Mechanisms and applications of apolipoproteins and apolipoprotein mimetic peptides: Common pathways in cardiovascular disease and cancer","authors":"Samuel C. Delk ,&nbsp;Faheem W. Gurgis ,&nbsp;Srinivasa T. Reddy","doi":"10.1016/j.semcancer.2025.05.006","DOIUrl":"10.1016/j.semcancer.2025.05.006","url":null,"abstract":"<div><div>Apolipoproteins are the defining functional component of lipoproteins and play critical roles in lipid transport and metabolism. High-density lipoprotein (HDL) and its primary functional constituent, apolipoprotein A-I, are of particular importance because of anti-inflammatory and antioxidant properties. Apolipoprotein mimetic peptides are short-chain amino acids designed to mimic the functions and alpha-helical structure of endogenous apolipoproteins and have demonstrated efficacy in ameliorating animal models of cardiovascular disease (CVD) and cancer. The mechanisms underlying the mimetics are yet to be fully elucidated, but a comprehensive review of the literature suggests that the peptides attack pathways shared in the pathophysiology of both diseases. This review also discusses the many pre-clinical studies on the mimetic peptides, highlighting possible mechanisms at work in each. Proposed mechanisms of protection against CVD and cancer include binding and removal of pro-inflammatory oxidized lipids, reduction in reactive oxygen species, and modulation of immune cell populations. Additionally, nanoparticles (NP) formulations incorporating apolipoprotein mimetic peptides or recombinant apolipoproteins have exhibited anti-atherogenic and anti-cancer activity. To date, clinical trials to assess the effect of reconstituted HDL NPs on CVD outcomes have not shown significant improvement. The large body of successful animal studies on apolipoproteins and apolipoprotein mimetic peptides presents a disconnect between pre-clinical and clinical efficacy, highlighting the need for a more complete understanding of the underlying pathways and mechanisms.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 74-84"},"PeriodicalIF":12.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045926","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 pancreatic cancer screening by identification of pathogenic variants of BRCA2/ BRCA1 in healthy individuals who have no known family history of pancreatic cancer: The arguments for and against.","authors":"Julie Earl ,&nbsp;Agapi Kataki ,&nbsp;Federico Canzian ,&nbsp;Eithne Costello ,&nbsp;Daniele Campa ,&nbsp;William Greenhalf","doi":"10.1016/j.semcancer.2025.05.001","DOIUrl":"10.1016/j.semcancer.2025.05.001","url":null,"abstract":"<div><div>The majority of patients with pancreatic ductal adenocarcinoma (PDAC) are no longer suitable for treatment with curable intent at the time of diagnosis resulting in a 5-year survival of less than 10 %. Imaging of asymptomatic individuals could identify early cancers, but only with a risk of falsely identifying a benign lesion as malignant. Screening of an unselected population would result in far more such false positives than true early cancers. Selection before screening is therefore essential, but there are very few populations at high enough risk to make screening more beneficial than counterproductive. These populations include carriers of specific mutations in <em>BRCA2,</em> and arguably <em>BRCA1,</em> who have a family history of PDAC. These pathogenic mutations all have a predictable effect in making loss of Homologous Recombination Repair (HRR) likely in a carrier’s lifetime. In this review the impact of such loss of HRR function on the likelihood of PDAC development will be discussed. Furthermore, it will be discussed whether the identification of a germline pathogenic mutation is sufficient to justify carrier surveillance for the development of the malignancy, or whether the current practice of screening only those carriers with a close relative diagnosed with PDAC is justifiable, as only a proportion of carriers are at high risk. The review will go beyond this to discuss whether there is an essential need to better define and stratify those at high risk, so that only high-risk carriers are put on surveillance.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"113 ","pages":"Pages 1-8"},"PeriodicalIF":12.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928063","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":"Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers","authors":"Yuki Fujii ,&nbsp;Zahra Asadi ,&nbsp;Kamiya Mehla","doi":"10.1016/j.semcancer.2025.04.001","DOIUrl":"10.1016/j.semcancer.2025.04.001","url":null,"abstract":"<div><div>Cathepsins, a group of lysosomal peptidases, have traditionally been recognized as tumor facilitators. Recent research, however, highlights their critical role in orchestrating cancer and the tumor microenvironment (TME). Primality, cathepsins degrade extracellular matrix, enabling cancer cells to invade and metastasize, while also promoting vascular endothelial infiltration and subsequent angiogenesis. Additionally, cathepsins boost fibroblast growth, thereby supporting tumor progression. More importantly, cathepsins are pivotal in modulating immune cells within the TME by regulating their recruitment, antigen processing and presentation, differentiation, and cell death, primarily contributing to immune suppression. Given their overexpression in tumors and elevated levels in the circulation of cancer patients, it is crucial to consider the systemic effects of cathepsins. Although the comprehensive role of cathepsins in cancer patients’ bodies remains underexplored, they likely influence systemic immunity and inflammation, cellular metabolism, muscle wasting, and distant metastasis through their unique proteolytic functions. Notably, cathepsins also confer resistance to chemoradiotherapy by rewriting the cellular profile within the TME. In this context, promising results are emerging from studies combining cathepsin inhibitors with conventional therapies to suppress tumor development effectively. This review aims to decipher the cathepsin-driven networks within cancer cells and the TME, detailing their contribution to chemoradioresistance by reshaping both micro- and macroenvironments. Furthermore, we explore current and future perspectives on therapies targeting cathepsins’ interactions, offering insights into innovative treatment strategies.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"112 ","pages":"Pages 150-166"},"PeriodicalIF":12.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870470","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}