Obesity and cancer—the evidence is fattening up

Kaaks, Rudolf; Kühn, Tilman

doi:10.1038/nrendo.2014.168

Cited by 25 publications

(14 citation statements)

References 9 publications

(10 reference statements)

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“…There is strong evidence that obesity is associated with an increased risk of cancer, including PDAC [45][46][47][48][49][50][51][52]. A recent umbrella review of systematic reviews and meta-analyses described that the association between obesity and PDAC is supported by strong evidence [53].…”

Section: Obesity and Type 2 Diabetes Mellitus As Upstream Factors Of mentioning

confidence: 99%

KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops

Eibl

Rozengurt

2019

Seminars in Cancer Biology

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Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC. Additional genetic mutations and/or environmental, nutritional, and metabolic stressors, e.g. inflammation and obesity, are required for efficient PDAC formation with activation of KRAS downstream effectors. Multiple factors "upstream" of KRAS associated with obesity, including insulin resistance, inflammation, changes in gut microbiota and GI peptides, can enhance/modulate downstream signals. Multiple signaling networks and feedback loops "downstream" of KRAS have been described that respond to obesogenic diets. We propose that KRAS mutations potentiate a signaling network that is promoted by environmental factors. Specifically, we envisage that KRAS mutations increase the intensity and duration of the growth-promoting signaling network. As the transcriptional activator YAP plays a critical role in the network, we conclude that the rationale for targeting the network (at different points), e.g. with FDA approved drugs such as statins and metformin, is therefore compelling.

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Section: Obesity and Type 2 Diabetes Mellitus As Upstream Factors Of mentioning

confidence: 99%

KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops

Eibl

Rozengurt

2019

Seminars in Cancer Biology

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“…Obesity is a well-defined risk factor for several cancer types and is associated with poorer outcomes for some tumor subsets [11][12][13][14]. The complex molecular mechanisms underlying the cancer-obesity link, also defined as "adiponcosis", are not fully understood [15].…”

Section: Introductionmentioning

confidence: 99%

The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective

Brocco

Florio

Lellis

et al. 2020

Cancers

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Pancreatic cancer (PC) is a lethal malignancy with rising incidence and limited therapeutic options. Obesity is a well-established risk factor for PC development. Moreover, it negatively affects outcome in PC patients. Excessive fat accumulation in obese, over- and normal-weight individuals induces metabolic and inflammatory changes of adipose tissue microenvironment leading to a dysfunctional adipose “organ”. This may drive the association between abnormal fat accumulation and pancreatic cancer. In this review, we describe several molecular mechanisms that underpin this association at both local and systemic levels. We focus on the role of adipose tissue-derived circulating factors including adipokines, hormones and pro-inflammatory cytokines, as well as on the impact of the local adipose tissue in promoting PC. A discussion on potential therapeutic interventions, interfering with pro-tumorigenic effects of dysfunctional adipose tissue in PC, is included. Considering the raise of global obesity, research efforts to uncover the molecular basis of the relationship between pancreatic cancer and adipose tissue dysfunction may provide novel insights for the prevention of this deadly disease. In addition, these efforts may uncover novel targets for personalized interventional strategies aimed at improving the currently unsatisfactory PC therapeutic options.

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“…Considering the high prevalence of obesity worldwide, a detailed understanding of how obesity promotes PDAC progression is of critical importance and would enable the development of interceptive strategies. Several mechanisms have been implicated in how obesity may accelerate cancer development and growth, including chronic inflammation, insulin resistance with hyperinsulinemia, altered adipokine production and sex hormone metabolism, gut dysbiosis, dietary factors, and alteration of the immune response to transformed cells [23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Teper

Eibl

2020

Cancers

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Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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Obesity and cancer—the evidence is fattening up

Cited by 25 publications

References 9 publications

KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops

KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops

The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

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