The molecular link between obesity and genomic instability in cancer development

An, Clemens; Pipia, Ilissa; Ruiz, Ana-Sofia; Argüelles, Ivonne; An, Martino; Wase, Saima; Peng, Guang

doi:10.1016/j.canlet.2022.216035

Cited by 7 publications

(7 citation statements)

References 69 publications

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“…Obesity can also alter the function and phenotype of the innate immune system, which may affect the exposure of complex drugs 106–109 . Obesity also has direct and indirect effects on tumor biology, which alter the development of cancer and response to therapy 32,34 . These factors can then change the therapeutic index, efficacy, and toxicities of anticancer agents.…”

Section: Discussionmentioning

confidence: 99%

“…Distinct classes of bioactive molecules are released by the adipose tissue, including peptide hormones, cytokines, enzymes, complement factors, growth factors, and chemokines (collectively referred to here as “adipokines”), and bioactive lipids (known as “lipokines”), which influence the metabolic, inflammatory, and immune landscape in normal physiology and disease 25,30,31 . Therefore, an altered adipose tissue secretory profile can affect core physiologic processes, locally or systemically, through an intricate signaling communication network, which includes not only classical adipokines and lipokines but also other mediators released by the adipose tissue, such as metabolites, noncoding RNAs, and exosomes 25,32–34 …”

Section: Effect Of Obesity On Tumor Biology Development Of Cancer And...mentioning

confidence: 99%

“…25,30,31 Therefore, an altered adipose tissue secretory profile can affect core physiologic processes, locally or systemically, through an intricate signaling communication network, which includes not only classical adipokines and lipokines but also other mediators released by the adipose tissue, such as metabolites, noncoding RNAs, and exosomes. 25,[32][33][34] At the center of the adipose tissue regulatory network, adipokines represent an expanding class of cell signaling molecules that play a key role in energy homeostasis, inflammation, and immune response. Adipokines can act in autocrine, paracrine, or endocrine manner and display proinflammatory and/or anti-inflammatory functions, although most promote inflammation.…”

Section: Effect Of Obesity On Tumor Biology Development Of Cancer And...mentioning

confidence: 99%

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Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Zamboni,

Charlab,

Burckart

et al. 2023

The Journal of Clinical Pharma

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An objective of the Precision Medicine Initiative, launched in 2015 by the US Food and Drug Administration and National Institutes of Health, is to optimize and individualize dosing of drugs, especially anticancer agents, with high pharmacokinetic and pharmacodynamic variability. The American Society of Clinical Oncology recently reported that 40% of obese patients receive insufficient chemotherapy doses and exposures, which may lead to reduced efficacy, and recommended pharmacokinetic studies to guide appropriate dosing in these patients. These issues will only increase in importance as the incidence of obesity in the population increases. This publication reviews the effects of obesity on (1) tumor biology, development of cancer, and antitumor response; (2) pharmacokinetics and pharmacodynamics of small‐molecule anticancer drugs; and (3) pharmacokinetics and pharmacodynamics of complex anticancer drugs, such as carrier‐mediated agents and biologics. These topics are not only important from a scientific research perspective but also from a drug development and regulator perspective. Thus, it is important to evaluate the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents in all categories of body habitus and especially in patients who are obese and morbidly obese. As the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents may be highly variable across drug types, the optimal dosing metric and algorithm for difference classes of drugs may be widely different. Thus, studies are needed to evaluate current and novel metrics and methods for measuring body habitus as related to optimizing the dose and reducing pharmacokinetic and pharmacodynamic variability of anticancer agents in patients who are obese and morbidly obese.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Obesity On Tumor Biology Development Of Cancer And...mentioning

confidence: 99%

Section: Effect Of Obesity On Tumor Biology Development Of Cancer And...mentioning

confidence: 99%

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Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Zamboni,

Charlab,

Burckart

et al. 2023

The Journal of Clinical Pharma

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“…The complex molecular link among insulin resistance, diabetes, obesity, genomic instability and cancer has been described [ 116 , 117 ]. Punicalgin, a hydrolyzable tannin isolated from pomegranate juice, has been found to ameliorate high-fat diet-induced insulin resistance, hepatic glucose and fatty acid metabolism disturbances, and damage to the liver by inhibiting the IKKβ/NF-κB inflammation route, controlling the intestinal microbiota equilibrium, and enhancing hepatic autophagy activity [ 118 ].…”

Section: Implication Of Autophagy In the Commonalities Between Autoim...mentioning

confidence: 99%

Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy

Műzes

Sípos

2023

Biomedicines

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The immune system and autophagy share a functional relationship. Both innate and adaptive immune responses involve autophagy and, depending on the disease’s origin and pathophysiology, it may have a detrimental or positive role on autoimmune disorders. As a “double-edged sword” in tumors, autophagy can either facilitate or impede tumor growth. The autophagy regulatory network that influences tumor progression and treatment resistance is dependent on cell and tissue types and tumor stages. The connection between autoimmunity and carcinogenesis has not been sufficiently explored in past studies. As a crucial mechanism between the two phenomena, autophagy may play a substantial role, though the specifics remain unclear. Several autophagy modifiers have demonstrated beneficial effects in models of autoimmune disease, emphasizing their therapeutic potential as treatments for autoimmune disorders. The function of autophagy in the tumor microenvironment and immune cells is the subject of intensive study. The objective of this review is to investigate the role of autophagy in the simultaneous genesis of autoimmunity and malignancy, shedding light on both sides of the issue. We believe our work will assist in the organization of current understanding in the field and promote additional research on this urgent and crucial topic.

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“…The role of adipokines in promoting genomic instability linking obesity and cancer has not been fully elucidated [ 61 ]. Altered microRNA secretion in adipose tissue may be implicated in oncogenesis [ 62 ], e.g., the exposure of prostate cancer cells to leptin downregulated the expression of micro-RNA-628 and led to increased cancer cell proliferation [ 63 ].…”

Section: The Association Of Sarcopenia Obesity and Sarcopenic Obesity...mentioning

confidence: 99%

The Modulation of Adipokines, Adipomyokines, and Sleep Disorders on Carcinogenesis

Brzecka

Martynowicz

Daroszewski

et al. 2023

JCM

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Obesity and sarcopenia, i.e., decreased skeletal muscle mass and function, are global health challenges. Moreover, people with obesity and sedentary lifestyles often have sleep disorders. Despite the potential associations, metabolic disturbances linking obesity, sarcopenia, and sleep disorders with cancer are neither well-defined nor understood fully. Abnormal levels of adipokines and adipomyokines originating from both adipose tissue and skeletal muscles are observed in some patients with obesity, sarcopenia and sleep disorders, as well as in cancer patients. This warrants investigation with respect to carcinogenesis. Adipokines and adipomyokines may exert either pro-carcinogenic or anti-carcinogenic effects. These factors, acting independently or together, may significantly modulate the incidence and progression of cancer. This review indicates that one of the possible pathways influencing the development of cancer may be the mutual relationship between obesity and/or sarcopenia, sleep quantity and quality, and adipokines/adipomyokines excretion. Taking into account the high proportion of persons with obesity and sedentary lifestyles, as well as the associations of these conditions with sleep disturbances, more attention should be paid to the individual and combined effects on cancer pathophysiology.

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The molecular link between obesity and genomic instability in cancer development

Cited by 7 publications

References 69 publications

Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents

Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy

The Modulation of Adipokines, Adipomyokines, and Sleep Disorders on Carcinogenesis

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