Pub Date : 2025-09-01Epub Date: 2025-06-13DOI: 10.1016/j.semcancer.2025.06.003
Yusha Wang , Jing Huang , Huan Tong , Yuting Jiang , Yu Jiang , Xuelei Ma
The gut microbiota is essential in colorectal cancer (CRC) development, progression, and therapeutic responsiveness through its metabolic acquisitions and immunomodulatory functions. The composition of gut microbiota is shaped by habitat filters such as oxygen availability, dietary components, and host-derived factors, which influence both bacterial colonization and metabolic strategies. Furthermore, microbial metabolism of carbohydrates, proteins, and lipids produces metabolites, including short-chain fatty acids (SCFAs), polyamines, ammonia, hydrogen sulfide, and secondary bile acids (BAs). These microbial metabolites can either support anti-tumor immune surveillance or promote tumorigenesis depending on their type, concentration, and the host context. Consequently, interventions such as high-fiber diets, prebiotic and probiotic supplementation, and fecal microbiota transplantation (FMT) have emerged as promising strategies to reshape the gut ecosystem and improve CRC treatment efficacy. This review summarizes current insights into microbial nutrient metabolism, discusses the immune-regulatory effects of key microbial metabolites, and explores microbiota-targeted strategies for enhancing antitumor efficacy. Understanding these interactions offers new therapeutic opportunities for cancer prevention and treatment.
{"title":"Nutrient acquisition of gut microbiota: Implications for tumor immunity","authors":"Yusha Wang , Jing Huang , Huan Tong , Yuting Jiang , Yu Jiang , Xuelei Ma","doi":"10.1016/j.semcancer.2025.06.003","DOIUrl":"10.1016/j.semcancer.2025.06.003","url":null,"abstract":"<div><div>The gut microbiota is essential in colorectal cancer (CRC) development, progression, and therapeutic responsiveness through its metabolic acquisitions and immunomodulatory functions. The composition of gut microbiota is shaped by habitat filters such as oxygen availability, dietary components, and host-derived factors, which influence both bacterial colonization and metabolic strategies. Furthermore, microbial metabolism of carbohydrates, proteins, and lipids produces metabolites, including short-chain fatty acids (SCFAs), polyamines, ammonia, hydrogen sulfide, and secondary bile acids (BAs). These microbial metabolites can either support anti-tumor immune surveillance or promote tumorigenesis depending on their type, concentration, and the host context. Consequently, interventions such as high-fiber diets, prebiotic and probiotic supplementation, and fecal microbiota transplantation (FMT) have emerged as promising strategies to reshape the gut ecosystem and improve CRC treatment efficacy. This review summarizes current insights into microbial nutrient metabolism, discusses the immune-regulatory effects of key microbial metabolites, and explores microbiota-targeted strategies for enhancing antitumor efficacy. Understanding these interactions offers new therapeutic opportunities for cancer prevention and treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 88-103"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302736","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 : 2025-09-01Epub Date: 2025-06-11DOI: 10.1016/j.semcancer.2025.06.007
Amal Jeiroshi , Juan Deng , Ziyao Xu , Annalisa Comandatore , Geng Xu , Antonino Glaviano , Luca Morelli , Ingrid Garajova , Elisa Giovannetti
Cellular senescence, described as a mechanism of irreversible cell cycle arrest, has emerged as a complex and multifaceted process with significant implications in cancer biology, particularly in pancreatic ductal adenocarcinoma (PDAC). This literature review aims to explore the intricate role of senescence in PDAC, focusing on its dual nature during tumorigenesis, in addition to therapy resistance, and its potential as a therapeutic target. Senescence escape was found to play a crucial role in PDAC progression, prompting the development of various pro-senescence therapies. However, recent studies have revealed a paradoxical aspect of the senescence-associated secretory phenotype, revealing its pro-tumorigenic effects and contribution to immune evasion in PDAC. By integrating insights from recent molecular studies, this review synthesizes current knowledge on the role of senescence in PDAC tumorigenesis and chemoresistance, with an emphasis on the emerging role of the tumor microenvironment and explores current and promising avenues for future research and potential therapeutic interventions.
{"title":"Navigating the paradox of senescence and chemoresistance in pancreatic cancer","authors":"Amal Jeiroshi , Juan Deng , Ziyao Xu , Annalisa Comandatore , Geng Xu , Antonino Glaviano , Luca Morelli , Ingrid Garajova , Elisa Giovannetti","doi":"10.1016/j.semcancer.2025.06.007","DOIUrl":"10.1016/j.semcancer.2025.06.007","url":null,"abstract":"<div><div>Cellular senescence, described as a mechanism of irreversible cell cycle arrest, has emerged as a complex and multifaceted process with significant implications in cancer biology, particularly in pancreatic ductal adenocarcinoma (PDAC). This literature review aims to explore the intricate role of senescence in PDAC, focusing on its dual nature during tumorigenesis, in addition to therapy resistance, and its potential as a therapeutic target. Senescence escape was found to play a crucial role in PDAC progression, prompting the development of various pro-senescence therapies. However, recent studies have revealed a paradoxical aspect of the senescence-associated secretory phenotype, revealing its pro-tumorigenic effects and contribution to immune evasion in PDAC. By integrating insights from recent molecular studies, this review synthesizes current knowledge on the role of senescence in PDAC tumorigenesis and chemoresistance, with an emphasis on the emerging role of the tumor microenvironment and explores current and promising avenues for future research and potential therapeutic interventions.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 60-72"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294900","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}
Deiodinases are key regulators of Thyroid Hormone (TH) bioavailability, exerting a precise spatial and temporal control over T3 levels in peripheral tissues. By dynamically modulating TH activation and inactivation, deiodinases allow target organs to adapt TH signaling to physiological and pathological demands, highlighting their importance in both health and disease. In cancer, their dysregulated expression reprograms cellular metabolism and shapes the tumor microenvironment (TME). Type 3 deiodinase (D3), frequently upregulated in proliferative and hypoxic tumor regions, fosters cell proliferation and resistance to differentiation. Conversely, type 2 deiodinase (D2) sustains glycolytic metabolism, angiogenesis, and redox disbalance, particularly in aggressive and p53-deficient tumors. Beyond cancer cells, deiodinases activity influences stromal and immune compartments, impacting glutamine metabolism and immune cell plasticity. This complex endocrine-metabolic axis supports tumor adaptation to stress and contributes to the emergence of resistance to therapy. Recent advances reveal the potential of targeting deiodinases to counteract cancer metabolic reprogramming and re-sensitize tumors to treatment. Given the essential and multifaceted roles of deiodinases in cancer biology, a comprehensive understanding of their mechanisms of action, regulation, and clinical implications is critical. This review aims to summarize current knowledge on the roles of deiodinases in cancer metabolism and immunity, focusing on their biochemical properties, regulatory networks, tissue-specific functions, and contributions to disease. In doing so, we seek to highlight emerging concepts in local TH signaling and explore potential avenues for therapeutic intervention targeting deiodinase pathways in precision oncology.
{"title":"The role of deiodinases on metabolic alteration in cancer","authors":"Caterina Miro , Annunziata Gaetana Cicatiello , Monica Dentice , Annarita Nappi","doi":"10.1016/j.semcancer.2025.07.003","DOIUrl":"10.1016/j.semcancer.2025.07.003","url":null,"abstract":"<div><div>Deiodinases are key regulators of Thyroid Hormone (TH) bioavailability, exerting a precise spatial and temporal control over T3 levels in peripheral tissues. By dynamically modulating TH activation and inactivation, deiodinases allow target organs to adapt TH signaling to physiological and pathological demands, highlighting their importance in both health and disease. In cancer, their dysregulated expression reprograms cellular metabolism and shapes the tumor microenvironment (TME). Type 3 deiodinase (D3), frequently upregulated in proliferative and hypoxic tumor regions, fosters cell proliferation and resistance to differentiation. Conversely, type 2 deiodinase (D2) sustains glycolytic metabolism, angiogenesis, and redox disbalance, particularly in aggressive and p53-deficient tumors. Beyond cancer cells, deiodinases activity influences stromal and immune compartments, impacting glutamine metabolism and immune cell plasticity. This complex endocrine-metabolic axis supports tumor adaptation to stress and contributes to the emergence of resistance to therapy. Recent advances reveal the potential of targeting deiodinases to counteract cancer metabolic reprogramming and re-sensitize tumors to treatment. Given the essential and multifaceted roles of deiodinases in cancer biology, a comprehensive understanding of their mechanisms of action, regulation, and clinical implications is critical. This review aims to summarize current knowledge on the roles of deiodinases in cancer metabolism and immunity, focusing on their biochemical properties, regulatory networks, tissue-specific functions, and contributions to disease. In doing so, we seek to highlight emerging concepts in local TH signaling and explore potential avenues for therapeutic intervention targeting deiodinase pathways in precision oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 215-226"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619968","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 : 2025-09-01Epub Date: 2025-07-25DOI: 10.1016/j.semcancer.2025.07.007
D.A. Lamabadusuriya , H. Jayasena , A.K. Bopitiya , A.D. De Silva , P. Jayasekera
Obesity is a growing global health challenge, significantly increasing the risk of metabolic diseases and cancer. This review explores the link between obesity-driven inflammation and cancer risk, emphasizing the key biological mechanisms. Chronic low-grade inflammation in obesity, mediated by dysfunctional adipose tissue, promotes a pro-tumorigenic microenvironment through increased secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. These factors contribute to insulin resistance, oxidative stress, and immune cell infiltration, fostering tumorigenesis. Adipokine imbalances, particularly elevated leptin and reduced adiponectin levels, further drive cancer progression by enhancing cell proliferation, angiogenesis, and immune evasion. Additionally, obesity-induced hypoxia, endoplasmic reticulum stress, and gut microbiome dysbiosis amplify systemic inflammation and metabolic dysfunction, further increasing cancer susceptibility. Epidemiological evidence highlights strong associations between obesity and cancers such as breast, colorectal, liver, and pancreatic cancer. Given the rising global prevalence of obesity, addressing inflammation-mediated oncogenesis is crucial. Lifestyle modifications, including weight loss through dietary and physical activity interventions, have demonstrated significant cancer risk reduction. Emerging pharmacological approaches targeting inflammatory pathways and adipokine regulation offer promising therapeutic potential. Understanding the mechanisms linking obesity, inflammation, and cancer provides valuable insights for developing targeted prevention and treatment strategies.
{"title":"Obesity-driven inflammation and cancer risk: A comprehensive review","authors":"D.A. Lamabadusuriya , H. Jayasena , A.K. Bopitiya , A.D. De Silva , P. Jayasekera","doi":"10.1016/j.semcancer.2025.07.007","DOIUrl":"10.1016/j.semcancer.2025.07.007","url":null,"abstract":"<div><div>Obesity is a growing global health challenge, significantly increasing the risk of metabolic diseases and cancer. This review explores the link between obesity-driven inflammation and cancer risk, emphasizing the key biological mechanisms. Chronic low-grade inflammation in obesity, mediated by dysfunctional adipose tissue, promotes a pro-tumorigenic microenvironment through increased secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. These factors contribute to insulin resistance, oxidative stress, and immune cell infiltration, fostering tumorigenesis. Adipokine imbalances, particularly elevated leptin and reduced adiponectin levels, further drive cancer progression by enhancing cell proliferation, angiogenesis, and immune evasion. Additionally, obesity-induced hypoxia, endoplasmic reticulum stress, and gut microbiome dysbiosis amplify systemic inflammation and metabolic dysfunction, further increasing cancer susceptibility. Epidemiological evidence highlights strong associations between obesity and cancers such as breast, colorectal, liver, and pancreatic cancer. Given the rising global prevalence of obesity, addressing inflammation-mediated oncogenesis is crucial. Lifestyle modifications, including weight loss through dietary and physical activity interventions, have demonstrated significant cancer risk reduction. Emerging pharmacological approaches targeting inflammatory pathways and adipokine regulation offer promising therapeutic potential. Understanding the mechanisms linking obesity, inflammation, and cancer provides valuable insights for developing targeted prevention and treatment strategies.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 256-266"},"PeriodicalIF":15.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718374","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 : 2025-09-01Epub Date: 2025-06-03DOI: 10.1016/j.semcancer.2025.06.002
Ludovica Verde , Martina Galasso , Silvia Savastano , Annamaria Colao , Luigi Barrea , Giovanna Muscogiuri
Obesity-related cancers are increasing globally, driven by metabolic disturbances and circadian rhythm disruptions. Circadian rhythms regulate physiological processes, and their misalignment has been linked to increased cancer risk. Chrononutrition, which aligns dietary intake with the body's circadian clock, has emerged as a potential strategy for cancer prevention and treatment. This review explored the intricate relationship between circadian rhythm, metabolism, and cancer, highlighting the role of meal timing, macronutrient distribution, fasting, and ketogenic diets. Additionally, the potential synergy between chrononutrition and cancer therapies was discussed, emphasizing the need for personalized approaches. Future research should focus on integrating chrononutritional strategies into clinical practice to enhance treatment outcomes and improve quality of life in patients with obesity-related cancers.
{"title":"\"Time\" for obesity-related cancers: The role of chrononutrition in cancer prevention and treatment","authors":"Ludovica Verde , Martina Galasso , Silvia Savastano , Annamaria Colao , Luigi Barrea , Giovanna Muscogiuri","doi":"10.1016/j.semcancer.2025.06.002","DOIUrl":"10.1016/j.semcancer.2025.06.002","url":null,"abstract":"<div><div>Obesity-related cancers are increasing globally, driven by metabolic disturbances and circadian rhythm disruptions. Circadian rhythms regulate physiological processes, and their misalignment has been linked to increased cancer risk. Chrononutrition, which aligns dietary intake with the body's circadian clock, has emerged as a potential strategy for cancer prevention and treatment. This review explored the intricate relationship between circadian rhythm, metabolism, and cancer, highlighting the role of meal timing, macronutrient distribution, fasting, and ketogenic diets. Additionally, the potential synergy between chrononutrition and cancer therapies was discussed, emphasizing the need for personalized approaches. Future research should focus on integrating chrononutritional strategies into clinical practice to enhance treatment outcomes and improve quality of life in patients with obesity-related cancers.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 15-28"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231369","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}
Recurrence of IPMNs after surgical resection is defined as the reappearance of new cystic lesions, invasive carcinoma, or metastases, either in the remnant pancreas or other distant sites. The median 5-year cumulative incidence of residual pancreatic lesions is 10 % (range, 0–21 %) and this risk continues to increase even after five years, especially in patients with the presence of HGD at first surgery and a family history of pancreatic ductal adenocarcinoma (PDAC). The management algorithm for all IPMNs is described in the latest guidelines on IPMNs; the patient's general condition, comorbidities, and life expectancy should be considered as well in the surgical decision. All patients operated for IPMN, have a risk of developing metachronous pancreatic lesions, which may require further surgery. Therefore, postoperative surveillance should be continued until the patient is surgically fit. The primary objective of this review is to evaluate the current scientific evidence regarding the management and surveillance strategies in patients who have undergone surgery for IPMN. Secondarily, we assessed the definitions of recurrence after surgery and explored the clinical, pathological, and biomolecular factors which may influence the biologic behavior of IPMNs. The optimal surveillance strategy for resected IPMN remains a topic of ongoing debate. The presence of an enlarging mass, the increase of ductal diameter, extrapancreatic disease observed during postoperative CT scans were previously taken into account as possible recurrence indicators. Additionally, positive resection margins, tumor invasiveness, and lymph node involvement were previously correlated with recurrence, while the role of molecular biomarkers still needs to bevalidated. This underscores the importance of rigorous, long-term follow-up, with multimodal approach as recurrent IPMNs can be detected even more than five years post-surgery.
{"title":"Long-term recurrence of PDAC after resection for IPMN: A narrative review of the literature on clinical and biologic predictors","authors":"Annalisa Comandatore , Gregorio Di Franco , Ingrid Garajová , Afrodita Panaitescu , Fabio Ausania , Livia Giannessi , Niccoló Furbetta , Simone Guadagni , Anna Caterina Milanetto , Claudio Pasquali , Manuel Gentiluomo , Chiara Corradi , Volkan Adsay , Daniele Campa , Elisa Giovannetti , Luca Morelli","doi":"10.1016/j.semcancer.2025.06.001","DOIUrl":"10.1016/j.semcancer.2025.06.001","url":null,"abstract":"<div><div>Recurrence of IPMNs after surgical resection is defined as the reappearance of new cystic lesions, invasive carcinoma, or metastases, either in the remnant pancreas or other distant sites. The median 5-year cumulative incidence of residual pancreatic lesions is 10 % (range, 0–21 %) and this risk continues to increase even after five years, especially in patients with the presence of HGD at first surgery and a family history of pancreatic ductal adenocarcinoma (PDAC). The management algorithm for all IPMNs is described in the latest guidelines on IPMNs; the patient's general condition, comorbidities, and life expectancy should be considered as well in the surgical decision. All patients operated for IPMN, have a risk of developing metachronous pancreatic lesions, which may require further surgery. Therefore, postoperative surveillance should be continued until the patient is surgically fit. The primary objective of this review is to evaluate the current scientific evidence regarding the management and surveillance strategies in patients who have undergone surgery for IPMN. Secondarily, we assessed the definitions of recurrence after surgery and explored the clinical, pathological, and biomolecular factors which may influence the biologic behavior of IPMNs. The optimal surveillance strategy for resected IPMN remains a topic of ongoing debate. The presence of an enlarging mass, the increase of ductal diameter, extrapancreatic disease observed during postoperative CT scans were previously taken into account as possible recurrence indicators. Additionally, positive resection margins, tumor invasiveness, and lymph node involvement were previously correlated with recurrence, while the role of molecular biomarkers still needs to bevalidated. This underscores the importance of rigorous, long-term follow-up, with multimodal approach as recurrent IPMNs can be detected even more than five years post-surgery.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 1-14"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222264","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 : 2025-09-01Epub Date: 2025-07-05DOI: 10.1016/j.semcancer.2025.07.001
Maria Isabela Bloise Alves Caldas Sawada , Monique de Fatima de Mello Santana , Milena Gomes Vancini , Marisa Passarelli
Plasma lipid and lipoprotein profiles are recognized as key modulators in breast cancer (BC) development. Notably, the association between high-density lipoprotein cholesterol (HDLc) and BC remains controversial, with studies reporting positive, negative, or no correlation. This inconsistency may arise from the clinical metrics used to quantify high-density lipoproteins (HDL), such as HDLc and apolipoprotein (apo) A-1, which may not accurately reflect HDL functionality in modulating the tumor microenvironment. Moreover, HDL particles isolated from plasma may undergo modifications influenced by tumor activity, varying with disease stage, severity, and treatment. In this review, we are critically reopening Pandora´s box analyzing evidence on HDLc plasma levels and HDL functionality in BC. Specifically, HDL contributes to tumor regulation by removing excess cellular cholesterol, thereby limiting sterol availability for cell replication and metastasis. Additionally, HDL exerts antioxidant and anti-inflammatory effects and acts as a carrier of bioactive proteins, lipids, and microRNAs, facilitating their delivery to target cells and modulating intracellular signaling and gene expression. Collectively, HDL functionality may serve as a predictor of therapeutic response and clinical outcomes in BC.
{"title":"Reopening Pandora’s box: Is there a role for HDL in breast cancer?","authors":"Maria Isabela Bloise Alves Caldas Sawada , Monique de Fatima de Mello Santana , Milena Gomes Vancini , Marisa Passarelli","doi":"10.1016/j.semcancer.2025.07.001","DOIUrl":"10.1016/j.semcancer.2025.07.001","url":null,"abstract":"<div><div>Plasma lipid and lipoprotein profiles are recognized as key modulators in breast cancer (BC) development. Notably, the association between high-density lipoprotein cholesterol (HDLc) and BC remains controversial, with studies reporting positive, negative, or no correlation. This inconsistency may arise from the clinical metrics used to quantify high-density lipoproteins (HDL), such as HDLc and apolipoprotein (apo) A-1, which may not accurately reflect HDL functionality in modulating the tumor microenvironment. Moreover, HDL particles isolated from plasma may undergo modifications influenced by tumor activity, varying with disease stage, severity, and treatment. In this review, we are critically reopening Pandora´s box analyzing evidence on HDLc plasma levels and HDL functionality in BC. Specifically, HDL contributes to tumor regulation by removing excess cellular cholesterol, thereby limiting sterol availability for cell replication and metastasis. Additionally, HDL exerts antioxidant and anti-inflammatory effects and acts as a carrier of bioactive proteins, lipids, and microRNAs, facilitating their delivery to target cells and modulating intracellular signaling and gene expression. Collectively, HDL functionality may serve as a predictor of therapeutic response and clinical outcomes in BC.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 227-241"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584724","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 : 2025-09-01Epub Date: 2025-05-22DOI: 10.1016/j.semcancer.2025.05.011
George Xie , Sho Okuda , Jing-Yan Gao , Timothy Wu , Jessica Jeong , Kun Ping Lu , Xiao Zhen Zhou
The prolyl-isomerase Pin1 is a unique enzyme that catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs. These motifs are present in many proteins, where isomerization of the typically rigid prolyl-peptide bond can lead to conformational changes, and subsequently regulate activity, stability, or localization. The specificity of Pin1 for phosphorylated motifs allows it to serve as a master regulator of proteins after phosphorylation, adding an additional layer of regulation to intricately control cellular signaling. As such, Pin1 plays an expansive role in numerous cancer and age-related signaling pathways, and is recognized as a major driver of cancer and promising therapeutic target. In this review, we discuss the role of Pin1 in regulation of age-related cancer signaling pathways, and we highlight the early development and current landscape of Pin1 inhibitors, and the prospect of Pin1 inhibition for cancer therapy.
{"title":"The central role of Pin1 in age-related cancer signaling pathways","authors":"George Xie , Sho Okuda , Jing-Yan Gao , Timothy Wu , Jessica Jeong , Kun Ping Lu , Xiao Zhen Zhou","doi":"10.1016/j.semcancer.2025.05.011","DOIUrl":"10.1016/j.semcancer.2025.05.011","url":null,"abstract":"<div><div>The prolyl-isomerase Pin1 is a unique enzyme that catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs. These motifs are present in many proteins, where isomerization of the typically rigid prolyl-peptide bond can lead to conformational changes, and subsequently regulate activity, stability, or localization. The specificity of Pin1 for phosphorylated motifs allows it to serve as a master regulator of proteins after phosphorylation, adding an additional layer of regulation to intricately control cellular signaling. As such, Pin1 plays an expansive role in numerous cancer and age-related signaling pathways, and is recognized as a major driver of cancer and promising therapeutic target. In this review, we discuss the role of Pin1 in regulation of age-related cancer signaling pathways, and we highlight the early development and current landscape of Pin1 inhibitors, and the prospect of Pin1 inhibition for cancer therapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 173-194"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143452","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 : 2025-09-01Epub Date: 2025-06-08DOI: 10.1016/j.semcancer.2025.06.005
Sandra Vladimirov , Marija Tomasevic , Nemanja Popov , Jelena Munjas , David de Gonzalo-Calvo , Miron Sopic
Cancer and atherosclerotic cardiovascular disease (ASCVD) are the main causes of mortality worldwide. The complex relationship between these two diseases has long puzzled scientists, with lipid metabolism emerging as a promising area for research and therapy of both diseases. Cholesterol accumulation promotes the formation of atherosclerotic plaques, while dysregulated lipid metabolism favours the progression of tumours. MicroRNAs (miRNAs) have been identified as key post-transcriptional regulators of lipid metabolism, influencing cholesterol synthesis and efflux, fatty acid oxidation and lipoprotein function. MiR-33, miR-144 and miR-122 modulate important target proteins such as sterol regulatory element-binding proteins (SREBPs), ATP-binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor gamma (PPARγ) and thus control metabolic reprogramming in both cancer and ASCVD. In cancer, miRNA-mediated lipid reprogramming promotes proliferation, immune evasion and metastasis, whereas dysregulated miRNAs in ASCVD contribute to foam cell formation, chronic inflammation and vascular dysfunction. The dual role of miRNAs, acting either as tumour suppressors or oncogenes, highlights their complex impact on lipid-related pathophysiology. Moreover, miRNA-based therapeutic strategies, including antagomirs and miRNA mimics, hold promise for targeted intervention in both diseases, which could reduce ASCVD risk in cancer patients and improve long-term outcomes. Understanding the intricate interactions between miRNAs, lipid metabolism and disease progression provides new insights into the overlapping molecular mechanisms of cancer and ASCVD and opens new therapeutic opportunities in the field of cardio-oncology.
{"title":"The converging roles of microRNAs and lipid metabolism in atherosclerotic cardiovascular disease and cancer","authors":"Sandra Vladimirov , Marija Tomasevic , Nemanja Popov , Jelena Munjas , David de Gonzalo-Calvo , Miron Sopic","doi":"10.1016/j.semcancer.2025.06.005","DOIUrl":"10.1016/j.semcancer.2025.06.005","url":null,"abstract":"<div><div>Cancer and atherosclerotic cardiovascular disease (ASCVD) are the main causes of mortality worldwide. The complex relationship between these two diseases has long puzzled scientists, with lipid metabolism emerging as a promising area for research and therapy of both diseases. Cholesterol accumulation promotes the formation of atherosclerotic plaques, while dysregulated lipid metabolism favours the progression of tumours. MicroRNAs (miRNAs) have been identified as key post-transcriptional regulators of lipid metabolism, influencing cholesterol synthesis and efflux, fatty acid oxidation and lipoprotein function. MiR-33, miR-144 and miR-122 modulate important target proteins such as sterol regulatory element-binding proteins (SREBPs), ATP-binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor gamma (PPARγ) and thus control metabolic reprogramming in both cancer and ASCVD. In cancer, miRNA-mediated lipid reprogramming promotes proliferation, immune evasion and metastasis, whereas dysregulated miRNAs in ASCVD contribute to foam cell formation, chronic inflammation and vascular dysfunction. The dual role of miRNAs, acting either as tumour suppressors or oncogenes, highlights their complex impact on lipid-related pathophysiology. Moreover, miRNA-based therapeutic strategies, including antagomirs and miRNA mimics, hold promise for targeted intervention in both diseases, which could reduce ASCVD risk in cancer patients and improve long-term outcomes. Understanding the intricate interactions between miRNAs, lipid metabolism and disease progression provides new insights into the overlapping molecular mechanisms of cancer and ASCVD and opens new therapeutic opportunities in the field of cardio-oncology.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 41-59"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267235","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 : 2025-09-01Epub Date: 2025-06-06DOI: 10.1016/j.semcancer.2025.06.004
Daniel Simancas-Racines , Claudia Reytor-González , Evelyn Frias-Toral , Christos S. Katsanos , Ricardo Hidalgo
This narrative review explores the influence of obesity on colorectal cancer, focusing on obesity-related factors, including chronic inflammation, metabolic dysregulation, and gut microbiota imbalance, which collectively create a pro-carcinogenic environment that increases colorectal cancer risk and complicates treatment outcomes. The findings indicate that obesity not only accelerates tumor progression but also presents challenges in colorectal cancer treatment, such as higher rates of surgical complications due to excess adipose tissue and altered pharmacokinetics that can reduce chemotherapy efficacy. Nutritional and lifestyle interventions, particularly weight management and anti-inflammatory nutritional therapies, are highlighted as effective strategies to reduce colorectal cancer risk and support treatment in patients with obesity. The study emphasizes the importance of personalized colorectal cancer treatment approaches for individuals with obesity and calls for public health policies targeting obesity prevention, which could significantly decrease colorectal cancer incidence and healthcare burdens associated with this high-risk population.
{"title":"Weighty matters: Unraveling the impact of obesity on colorectal cancer and nutritional interventions","authors":"Daniel Simancas-Racines , Claudia Reytor-González , Evelyn Frias-Toral , Christos S. Katsanos , Ricardo Hidalgo","doi":"10.1016/j.semcancer.2025.06.004","DOIUrl":"10.1016/j.semcancer.2025.06.004","url":null,"abstract":"<div><div>This narrative review explores the influence of obesity on colorectal cancer, focusing on obesity-related factors, including chronic inflammation, metabolic dysregulation, and gut microbiota imbalance, which collectively create a pro-carcinogenic environment that increases colorectal cancer risk and complicates treatment outcomes. The findings indicate that obesity not only accelerates tumor progression but also presents challenges in colorectal cancer treatment, such as higher rates of surgical complications due to excess adipose tissue and altered pharmacokinetics that can reduce chemotherapy efficacy. Nutritional and lifestyle interventions, particularly weight management and anti-inflammatory nutritional therapies, are highlighted as effective strategies to reduce colorectal cancer risk and support treatment in patients with obesity. The study emphasizes the importance of personalized colorectal cancer treatment approaches for individuals with obesity and calls for public health policies targeting obesity prevention, which could significantly decrease colorectal cancer incidence and healthcare burdens associated with this high-risk population.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 29-40"},"PeriodicalIF":12.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249453","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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