[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382775-105":59,"doc-detail-382775-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","decoding-the-obesitycancer-connection-lessons-from-preclinical-models-of-pancreatic-adenocarcinoma","Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma","","Obesity is an energy-excess metabolic state that raises risk for more than a dozen cancer types, yet the causal mechanisms linking weight gain to tumor initiation and early progression remain incompletely resolved. This review synthesizes preclinical model evidence using pancreatic adenocarcinoma as a paradigmatic example, explaining how obesity reshapes premalignant and tumor cells plus micro- and macroenvironments via altered metabolism, hormone dysregulation, inflammation, and microbial dysbiosis, while noting confounders and knowledge gaps, and outlining emerging modeling and analytic approaches for prevention and therapy strategies.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/decoding-the-obesitycancer-connection-lessons-from-preclinical-models-of-pancreatic-adenocarcinoma/382775/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/decoding-the-obesitycancer-connection-lessons-from-preclinical-models-of-pancreatic-adenocarcinoma/382775.png","ImageObject",300,407,{"name":92,"@type":93},"Rizky","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is obesity considered a driver of cancer development?","Question",{"text":113,"@type":114},"Obesity is linked to increased risk across more than a dozen cancer types and is associated with mechanistic changes in host physiology such as hormone dysregulation, insulin resistance, inflammation, and microbial dysbiosis that can promote tumor initiation and progression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why does the review use pancreatic adenocarcinoma as the main example?",{"text":118,"@type":114},"Pancreatic adenocarcinoma is presented as a paradigmatic obesity-driven cancer due to consistent epidemiologic links between BMI and PDAC risk, associations with metastasis and survival, limited benefit from targeted therapy and immunotherapy, and reliance on the KRAS hallmark oncogene in most cases.",{"name":120,"@type":111,"acceptedAnswer":121},"What specific mechanisms connect obesity to pancreatic tumorigenesis in the preclinical evidence?",{"text":122,"@type":114},"The review highlights evidence for altered cellular metabolism, hormone dysregulation, inflammation, and microbial dysbiosis, while also identifying variables that may confound interpretation of these preclinical studies and gaps in current knowledge.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},382775,1790484803,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962085564807,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Review  \nDecoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma  \nChristian F Ruiz1,2,*, Cathy Garcia1,2,*, Jeremy B Jacox1,2,3,*, Lauren Lawres4,*, Mandar D Muzumdar1,2,3,5   \nObesity is a metabolic state of energy excess and a risk factor for over a dozen cancer types. Because of the rising worldwide prevalence of obesity, decoding the mechanisms by which obesity promotes tumor initiation and early progression is a societal imperative and could broadly impact human health. Here, wereview results from preclinical models that link obesity to cancer, using pancreatic adenocarcinoma as a paradigmatic example. We discuss how obesity drives cancer development by reprogramming the pretumor or tumor cell and its micro- and macroenvironments. Specifically, we describe evidence for (1) altered cellular metabolism,(2) hormone dysregulation,(3) inflammation, and (4) microbial dysbiosis in obesity-driven pancreatic tumorigenesis, denoting variables that confound interpretation of these studies, and highlight remaining gaps in knowledge. Recent advances in preclinical modeling and emerging unbiased analytic approaches will aid in further unraveling the complex link between obesity and cancer, informing novel strategies for prevention, interception, and therapy in pancreatic adenocarcinoma and other obesity-associated cancers.  \nDOI 10.26508/lsa.202302228 | Received 20 June 2023 | Revised 15 August 2023 | Accepted 21 August 2023 | Published online 30 August 2023  \nIntroduction  \nObesity is a metabolic state of energy excess associated with systemic alterations in host physiology including hormone dysregulation, insulin resistance, inflammation, and microbial dysbiosis. Despite years of research, there remains a lack of consensus on the causes of energy imbalance in obesity, which include both host (e.g., genetics, gut microbes, sedentary lifestyle) and exogenous factors (e.g., diet, drugs, toxins) (Fig 1) . In contrast, there is little doubt that obesity plays a consequential role in numerous chronic diseases, spurring the World Health Organization and other major governmental health organizations to propose frameworks for obesity prevention. Although the impact of obesity on diabetes and cardiovascular disease is well established, it has become  \nincreasing clear that obesity is also a pathogenic driver of cancer. Indeed, obesity is associated with an increased risk of over a dozen cancer types, including nearly all cancers of the gastrointestinal tract (Lauby-Secretan et al, 2016), yet the mechanistic basis for these relationships remains incompletely understood. Given the rapid rise in the worldwide prevalence of obesity (Fig 2A), deciphering the mechanisms by which obesity promotes cancer development has become an urgent societal imperative that is likely to broadly impact human health.  \nIn this review, we enumerate these mechanisms by focusing on evidence garnered from preclinical mouse models of cancer. We center this discussion on pancreatic adenocarcinoma (PDAC), the predominant histologic subtype of pancreatic cancer and a leading cause of cancer-related death worldwide. We chose PDAC as a paradigmatic example of an obesity-driven cancer for several compelling reasons. First, epidemiologic studies over the last two decades have consistently shown a positive dose-dependent association between Body Mass Index (BMI), a measure of obesity, and PDAC risk (Michaud et al, 2001; Larsson et al, 2007; Arslan et al, 2010; Klein, 2021) . In fact, the continual rise in PDAC incidence is thought to be due, in large part, to a parallel increase in obesity rates, especially in younger individuals (Sung et al, 2019) . Furthermore, higher pre-diagnostic BMI has been associated with increased metastasis at diagnosis and decreased PDAC survival across all clinical stages (Calle et al, 2003; Li et al, 2009; Yuan et al, 2013; Kasenda et al, 2014), arguing that obesity may also drive progression to more advanc","cbCaiq5za30c1OT5","https://ap.wps.com/l/cbCaiq5za30c1OT5","pdf",1850448,17,"English","# Introduction\n## Obesity as a metabolic risk factor\n## Rationale for focusing on pancreatic adenocarcinoma\n## Mechanisms studied in preclinical mouse models","[{\"question\":\"Why is obesity considered a driver of cancer development?\",\"answer\":\"Obesity is linked to increased risk across more than a dozen cancer types and is associated with mechanistic changes in host physiology such as hormone dysregulation, insulin resistance, inflammation, and microbial dysbiosis that can promote tumor initiation and progression.\"},{\"question\":\"Why does the review use pancreatic adenocarcinoma as the main example?\",\"answer\":\"Pancreatic adenocarcinoma is presented as a paradigmatic obesity-driven cancer due to consistent epidemiologic links between BMI and PDAC risk, associations with metastasis and survival, limited benefit from targeted therapy and immunotherapy, and reliance on the KRAS hallmark oncogene in most cases.\"},{\"question\":\"What specific mechanisms connect obesity to pancreatic tumorigenesis in the preclinical evidence?\",\"answer\":\"The review highlights evidence for altered cellular metabolism, hormone dysregulation, inflammation, and microbial dysbiosis, while also identifying variables that may confound interpretation of these preclinical studies and gaps in current knowledge.\"}]","Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma | PDF",1790252353,43]