Pub Date : 2025-06-26DOI: 10.1016/j.semcancer.2025.06.010
Gerardo Sarno , Claudia Reytor-González , Evelyn Frias-Toral , Martín Campuzano-Donoso , Christos S. Katsanos , Daniel Simancas-Racines
Obesity significantly affects gastrointestinal cancer surgery outcomes by creating complex challenges throughout the preoperative, intraoperative, and postoperative stages. This narrative review explores the intricate relationship between obesity and GIC surgery, highlighting the dual burden of obesity as a global public health issue and a determinant of surgical complications. The review aims to analyze physiological and technical hurdles, including limited visibility, prolonged operative times, increased perioperative risks, and adverse recovery outcomes associated with obesity. Evidence emphasizes the critical role of excess visceral fat, systemic inflammation, and insulin resistance in elevating surgical risks. Mitigation strategies involve preoperative nutritional optimization, use of advanced surgical technologies such as robotic-assisted and laparoscopic systems, and individualized postoperative care, encompassing early mobilization, tailored pain management, and close monitoring of metabolic parameters. Despite advancements, knowledge gaps remain, particularly regarding sarcopenic obesity and the long-term impact of preoperative dietary interventions. Future research should focus on refining minimally invasive techniques, integrating personalized medicine, and exploring innovative perioperative protocols to address obesity-related risks effectively. By fostering a multidisciplinary approach, this review underscores the necessity for targeted interventions to enhance outcomes and improve the quality of care for patients with obesity undergoing gastrointestinal cancer surgery.
{"title":"Navigating the weight: The impact of obesity on gastrointestinal cancer surgery and strategies for improved outcomes","authors":"Gerardo Sarno , Claudia Reytor-González , Evelyn Frias-Toral , Martín Campuzano-Donoso , Christos S. Katsanos , Daniel Simancas-Racines","doi":"10.1016/j.semcancer.2025.06.010","DOIUrl":"10.1016/j.semcancer.2025.06.010","url":null,"abstract":"<div><div>Obesity significantly affects gastrointestinal cancer surgery outcomes by creating complex challenges throughout the preoperative, intraoperative, and postoperative stages. This narrative review explores the intricate relationship between obesity and GIC surgery, highlighting the dual burden of obesity as a global public health issue and a determinant of surgical complications. The review aims to analyze physiological and technical hurdles, including limited visibility, prolonged operative times, increased perioperative risks, and adverse recovery outcomes associated with obesity. Evidence emphasizes the critical role of excess visceral fat, systemic inflammation, and insulin resistance in elevating surgical risks. Mitigation strategies involve preoperative nutritional optimization, use of advanced surgical technologies such as robotic-assisted and laparoscopic systems, and individualized postoperative care, encompassing early mobilization, tailored pain management, and close monitoring of metabolic parameters. Despite advancements, knowledge gaps remain, particularly regarding sarcopenic obesity and the long-term impact of preoperative dietary interventions. Future research should focus on refining minimally invasive techniques, integrating personalized medicine, and exploring innovative perioperative protocols to address obesity-related risks effectively. By fostering a multidisciplinary approach, this review underscores the necessity for targeted interventions to enhance outcomes and improve the quality of care for patients with obesity undergoing gastrointestinal cancer surgery.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 138-149"},"PeriodicalIF":12.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519235","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}
Tumor immunotherapy has achieved revolutionary advancements; however, owing to the complex interplay of multiple intrinsic and extrinsic tumor factors, the patient response rate remains suboptimal. Recent research has emphasized the pivotal role of microbiome in tumor progression. Under normal physiological conditions, microbiome enter orally and colonize sites such as the oral and intestinal mucosa, establishing a dynamic microbiome equilibrium that participates in essential physiological processes, including host metabolism and immune regulation. However, in pathological states, including dysbiosis, tumor initiation, or compromised mucosal barrier function, the microbiome can penetrate the mucosal barrier, infiltrate tumor tissues, and engage in intricate direct or indirect interactions with immune cells. These interactions play a pivotal role in reshaping the tumor immune microenvironment and modulating the host's anti-tumor immune response. This review elaborate the regulatory mechanisms involved in direct and indirect interactions between microbiome and immune cells within tumors, and their implications for tumor immunotherapy. We discuss the external factors that impact these interactions and outline the potential use of engineered bacteria in cancer treatment. From the perspective of the interaction network between microbiomes and immune cells, this review elucidates the mechanisms and potential of microbiomes in tumor immunotherapy, offering new insights and potential targets for innovative strategies in tumor prevention and treatment.
{"title":"The microbiome-immune cell interaction network: Advancing tumor immunotherapy","authors":"Wei Liu, Zhou Lan, Zhenzi Lin, Yuyue Zhao, Junxiang Lian, Guangtao Yu","doi":"10.1016/j.semcancer.2025.06.009","DOIUrl":"10.1016/j.semcancer.2025.06.009","url":null,"abstract":"<div><div>Tumor immunotherapy has achieved revolutionary advancements; however, owing to the complex interplay of multiple intrinsic and extrinsic tumor factors, the patient response rate remains suboptimal. Recent research has emphasized the pivotal role of microbiome in tumor progression. Under normal physiological conditions, microbiome enter orally and colonize sites such as the oral and intestinal mucosa, establishing a dynamic microbiome equilibrium that participates in essential physiological processes, including host metabolism and immune regulation. However, in pathological states, including dysbiosis, tumor initiation, or compromised mucosal barrier function, the microbiome can penetrate the mucosal barrier, infiltrate tumor tissues, and engage in intricate direct or indirect interactions with immune cells. These interactions play a pivotal role in reshaping the tumor immune microenvironment and modulating the host's anti-tumor immune response. This review elaborate the regulatory mechanisms involved in direct and indirect interactions between microbiome and immune cells within tumors, and their implications for tumor immunotherapy. We discuss the external factors that impact these interactions and outline the potential use of engineered bacteria in cancer treatment. From the perspective of the interaction network between microbiomes and immune cells, this review elucidates the mechanisms and potential of microbiomes in tumor immunotherapy, offering new insights and potential targets for innovative strategies in tumor prevention and treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 128-137"},"PeriodicalIF":12.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480164","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 : 2025-06-20DOI: 10.1016/j.semcancer.2025.06.008
Miriam Lee-Rueckert , Matti Jauhiainen , Petri T. Kovanen , Joan Carles Escolà-Gil
An inflammatory and lipid-enriched tissue microenvironment is a common characteristic of the extracellular niches of affected tissues in atherosclerosis, cancer, and obesity. These respective interstitial environments appear to be induced by infiltration of plasma lipids and early local recruitment of monocyte-derived macrophages. In the tissue niches, the macrophages display remarkable phenotypic and functional plasticity and exert multifaceted roles in tissue homeostasis. Multiple local signaling events contribute to the phenotypic polarization of the tissue-resident macrophages into M1-like, M2-like, and multiple mixed subpopulations. This study aims to review and compare the roles of lipids and lipoproteins in shaping the inflammatory and lipid-enriched microenvironments of atherosclerotic arterial intima, malignant tumors, and obese adipose tissue, so generating dysfunctional macrophages. Circulating lipoprotein-bound lipids and albumin-bound fatty acids can cross the vascular endothelial barrier and infiltrate the interstitial fluids, resulting in variable levels of plasma-derived lipids, notably low-density lipoproteins (LDL), high-density lipoproteins (HDL), and locally generated small lipid-poor HDL species (preβ-HDL). Whilst LDL particles mainly supply liver-derived cholesterol to the cells of peripheral tissues, HDL particles can promote the reverse transfer of cellular cholesterol into the circulation and ultimately via the liver to the gut for its fecal excretion. Thus, the LDL/HDL ratio in the interstitial fluids can either promote or prevent cholesterol accumulation in the tissue-resident macrophages. Various types of peripheral cells modify interstitial LDL and HDL particles by oxidation, proteolysis, lipolysis, aggregation, or fusion, rendering them dysfunctional. By engulfing excessive amounts of extracellular lipids and modified LDL particles in such lipid-rich microenvironments, macrophages can become dysfunctional, a typical example being the atherosclerotic arterial intima. Similarly, tissue microenvironments characteristic of several malignant tumors and the obese adipose tissue are rich in triglyceride (TG)-rich lipoproteins and free fatty acids, inducing accumulation of TG and glycerophospholipids in the intracellular lipid droplets of macrophages. The lipid-loaded macrophages are currently considered novel markers for diagnosis and selective therapeutic targets not only in the arterial intima but also in malignant tumors and obese adipose tissue. Together, the available data identify potential roles of lipids and lipoproteins present in the interstitial fluids of the atherosclerotic arterial intima, malignant tumors, and obese adipose tissue in the generation of distinct lipid-loaded macrophage subpopulations and suggest their contributory roles in the development and progression of atherosclerosis, cancer, and obesity, the three major health concerns worldwide.
{"title":"Lipids and lipoproteins in the interstitial tissue fluid regulate the formation of dysfunctional tissue-resident macrophages: Implications for atherogenic, tumorigenic, and obesogenic processes","authors":"Miriam Lee-Rueckert , Matti Jauhiainen , Petri T. Kovanen , Joan Carles Escolà-Gil","doi":"10.1016/j.semcancer.2025.06.008","DOIUrl":"10.1016/j.semcancer.2025.06.008","url":null,"abstract":"<div><div>An inflammatory and lipid-enriched tissue microenvironment is a common characteristic of the extracellular niches of affected tissues in atherosclerosis, cancer, and obesity. These respective interstitial environments appear to be induced by infiltration of plasma lipids and early local recruitment of monocyte-derived macrophages. In the tissue niches, the macrophages display remarkable phenotypic and functional plasticity and exert multifaceted roles in tissue homeostasis. Multiple local signaling events contribute to the phenotypic polarization of the tissue-resident macrophages into M1-like, M2-like, and multiple mixed subpopulations. This study aims to review and compare the roles of lipids and lipoproteins in shaping the inflammatory and lipid-enriched microenvironments of atherosclerotic arterial intima, malignant tumors, and obese adipose tissue, so generating dysfunctional macrophages. Circulating lipoprotein-bound lipids and albumin-bound fatty acids can cross the vascular endothelial barrier and infiltrate the interstitial fluids, resulting in variable levels of plasma-derived lipids, notably low-density lipoproteins (LDL), high-density lipoproteins (HDL), and locally generated small lipid-poor HDL species (preβ-HDL). Whilst LDL particles mainly supply liver-derived cholesterol to the cells of peripheral tissues, HDL particles can promote the reverse transfer of cellular cholesterol into the circulation and ultimately via the liver to the gut for its fecal excretion. Thus, the LDL/HDL ratio in the interstitial fluids can either promote or prevent cholesterol accumulation in the tissue-resident macrophages. Various types of peripheral cells modify interstitial LDL and HDL particles by oxidation, proteolysis, lipolysis, aggregation, or fusion, rendering them dysfunctional. By engulfing excessive amounts of extracellular lipids and modified LDL particles in such lipid-rich microenvironments, macrophages can become dysfunctional, a typical example being the atherosclerotic arterial intima. Similarly, tissue microenvironments characteristic of several malignant tumors and the obese adipose tissue are rich in triglyceride (TG)-rich lipoproteins and free fatty acids, inducing accumulation of TG and glycerophospholipids in the intracellular lipid droplets of macrophages. The lipid-loaded macrophages are currently considered novel markers for diagnosis and selective therapeutic targets not only in the arterial intima but also in malignant tumors and obese adipose tissue. Together, the available data identify potential roles of lipids and lipoproteins present in the interstitial fluids of the atherosclerotic arterial intima, malignant tumors, and obese adipose tissue in the generation of distinct lipid-loaded macrophage subpopulations and suggest their contributory roles in the development and progression of atherosclerosis, cancer, and obesity, the three major health concerns worldwide.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 104-127"},"PeriodicalIF":12.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369211","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 : 2025-06-13DOI: 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":"2025-06-13","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 : 2025-06-13DOI: 10.1016/j.semcancer.2025.06.006
Emmanuel Jacobo-Tovar, Andrea Medel-Sánchez, Cosette Durán-Castillo, Rodolfo Guardado-Mendoza
Obesity-associated insulin resistance (IR) is characterized by a chronic low-grade inflammatory state driven by adipocyte dysfunction, elevated free fatty acids, and proinflammatory cytokines. These factors activate signaling pathways—including JNK, TLR, and NF-κB—that impair insulin receptor function and promote hyperinsulinemia. Elevated insulin reduces insulin-like growth factor binding proteins, thereby increasing the bioavailability of IGF-1 and IGF-2, which stimulate oncogenic pathways such as PI3K-AKT-mTOR and RAS-MAPK. Epidemiological evidence links IR to an increased risk of a broad spectrum of malignancies, though associations vary by cancer subtype, patient demographics, and tumor characteristics. Therapeutic strategies targeting IR—ranging from lifestyle interventions and weight reduction to pharmacological agents like metformin and GLP-1 receptor agonists—have shown promise in reducing cancer risk and improving prognosis. Metformin exhibits anticancer effects through both AMPK-dependent and independent mechanisms, including mTOR inhibition, suppression of cell proliferation, and attenuation of oxidative stress. While observational studies support a relationship between improved insulin sensitivity and reduced cancer risk, definitive evidence from interventional trials remains limited. Overall, these findings underscore the critical role of metabolic dysfunction in tumorigenesis and highlight the potential of IR-targeted therapies in cancer prevention and management.
{"title":"Thematic issue: Obesity-driven cancer: Clinical and molecular aspects","authors":"Emmanuel Jacobo-Tovar, Andrea Medel-Sánchez, Cosette Durán-Castillo, Rodolfo Guardado-Mendoza","doi":"10.1016/j.semcancer.2025.06.006","DOIUrl":"10.1016/j.semcancer.2025.06.006","url":null,"abstract":"<div><div>Obesity-associated insulin resistance (IR) is characterized by a chronic low-grade inflammatory state driven by adipocyte dysfunction, elevated free fatty acids, and proinflammatory cytokines. These factors activate signaling pathways—including JNK, TLR, and NF-κB—that impair insulin receptor function and promote hyperinsulinemia. Elevated insulin reduces insulin-like growth factor binding proteins, thereby increasing the bioavailability of IGF-1 and IGF-2, which stimulate oncogenic pathways such as PI3K-AKT-mTOR and RAS-MAPK. Epidemiological evidence links IR to an increased risk of a broad spectrum of malignancies, though associations vary by cancer subtype, patient demographics, and tumor characteristics. Therapeutic strategies targeting IR—ranging from lifestyle interventions and weight reduction to pharmacological agents like metformin and GLP-1 receptor agonists—have shown promise in reducing cancer risk and improving prognosis. Metformin exhibits anticancer effects through both AMPK-dependent and independent mechanisms, including mTOR inhibition, suppression of cell proliferation, and attenuation of oxidative stress. While observational studies support a relationship between improved insulin sensitivity and reduced cancer risk, definitive evidence from interventional trials remains limited. Overall, these findings underscore the critical role of metabolic dysfunction in tumorigenesis and highlight the potential of IR-targeted therapies in cancer prevention and management.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"114 ","pages":"Pages 73-87"},"PeriodicalIF":12.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302737","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 : 2025-06-11DOI: 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":"2025-06-11","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}
Pub 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":"2025-06-08","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 : 2025-06-06DOI: 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":"2025-06-06","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}
Pub 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":"2025-06-03","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":"2025-06-02","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}
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