Mechanistic Targets and Phytochemical Strategies for Breaking the Obesity-Cancer Link

The prevalence of obesity, an established risk and progression factor for many cancers, has increased dramatically in many countries over the past three decades. Worldwide, an estimated 600 million adults are currently obese. Thus, a better understanding of the mechanistic links between obesity and cancer is urgently needed to identify intervention targets and strategies to offset the procancer effects of obesity. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer association, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and perturbations in the tumor microenvironment. These interrelated pathways and processes that are aberrantly regulated in obese individuals represent mechanism-based targets for disrupting the obesity-cancer link using phytochemicals.

• Publication year

  2013

• Venue

  Frontiers in Oncology

• Publication date

  2013-07-16

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3389/fonc.2013.00209PMID 23967401PMCID 3746736
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A Global Perspective

  2015cited by this paper
• Preclinical and Clinical Studies

  2015cited by this paper
• an update on

  2014influential reference
• The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are reversed by RAD001

  2013cited by this paper
• Ursolic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in an Orthotopic Nude Mouse Model by Targeting Multiple Cell Signaling Pathways: Chemosensitization with Capecitabine

  2012cited by this paper
• Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity.

  2012cited by this paper
• The role of adiponectin in human vascular physiology.

  2012cited by this paper
• Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth by Targeting VEGFR- 2 Regulated AKT/mTOR/P70S6K Signaling Pathways

  2012cited by this paper
• Curcumin molecular targets in obesity and obesity-related cancers.

  2012cited by this paper
• PAI‐1, progress in understanding the clinical problem and its aetiology

  2012influential reference
• Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus.

  2012cited by this paper
• Dietary Energy Balance Modulates Epithelial-to-Mesenchymal Transition and Tumor Progression in Murine Claudin-Low and Basal-like Mammary Tumor Models

  2012cited by this paper
• Ursolic Acid Inhibits Cigarette Smoke Extract-Induced Human Bronchial Epithelial Cell Injury and Prevents Development of Lung Cancer

  2012cited by this paper
• Ursolic acid inhibits growth and induces apoptosis in gemcitabine-resistant human pancreatic cancer via the JNK and PI3K/Akt/NF-κB pathways.

  2012cited by this paper
• Plant natural compounds: targeting pathways of autophagy as anti‐cancer therapeutic agents

  2012cited by this paper
• The insulin and insulin-like growth factor receptor family in neoplasia: an update

  2012cited by this paper
• Role of nuclear factor-κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents

  2011cited by this paper
• Sixteen years and counting: an update on leptin in energy balance.

  2011cited by this paper
• The association between vascular endothelial growth factor expression in invasive breast cancer and survival varies with intrinsic subtypes and use of adjuvant systemic therapy: results from the Nurses’ Health Study

  2011cited by this paper
• Obesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland

  2011cited by this paper
• The Link between the Metabolic Syndrome and Cancer

  2011cited by this paper
• Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research.

  2010cited by this paper
• Prevalence and trends in obesity among US adults, 1999-2008.

  2010cited by this paper
• An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol.

  2010cited by this paper
• Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies

  2010cited by this paper
• The life span-prolonging effect of Sirtuin-1 is mediated by autophagy

  2010cited by this paper
• Antitumor Effects of Ursolic Acid in a Mouse Model of Postmenopausal Breast Cancer

  2010cited by this paper
• Energy balance, host-related factors, and cancer progression.

  2010cited by this paper
• A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival.

  2010cited by this paper
• Antiangiogenic Activity of Ursolic Acid

  2010cited by this paper
• Updates of mTOR inhibitors.

  2010cited by this paper
• Macrophages, inflammation, and insulin resistance.

  2010cited by this paper
• Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals.

  2010cited by this paper
• Targeting the PI3K signaling pathway in cancer.

  2010cited by this paper
• Interaction between adiponectin and leptin influences the risk of colorectal adenoma.

  2010cited by this paper
• Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management.

  2010cited by this paper
• Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006.

  2009cited by this paper
• Targeting the adiponectin:leptin ratio for postmenopausal breast cancer prevention.

  2009cited by this paper
• Circulating levels of leptin, adiposity and breast cancer risk

  2009cited by this paper
• Akt-dependent and -independent mechanisms of mTOR regulation in cancer.

  2009cited by this paper
• Obesity and Breast Cancer: The Roles of Peroxisome Proliferator-Activated Receptor-γ and Plasminogen Activator Inhibitor-1

  2009cited by this paper
• Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity.

  2009cited by this paper
• Inflammation in obesity-related diseases.

  2009cited by this paper
• The Vote of Acute Medical Inpatients

  2009cited by this paper
• Dietary Energy Balance Modulates Signaling through the Akt/Mammalian Target of Rapamycin Pathways in Multiple Epithelial Tissues

  2008cited by this paper
• Effects of adiponectin on breast cancer cell growth and signaling

  2008cited by this paper
• Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition

  2008cited by this paper
• The Yin‐Yang of tumor‐associated macrophages in neoplastic progression and immune surveillance

  2008cited by this paper
• Obesity and cancer: Pathophysiological and biological mechanisms

  2008cited by this paper
• Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women.

  2008cited by this paper
• The Prostate 68 : 1592 ^ 1598 ( 2008 ) Relationship Between SerumAdiponectin and ProstateCancerGrade

  2008cited by this paper
• Leptin receptor signaling and the regulation of mammalian physiology

  2008cited by this paper
• Angiogenesis modulates adipogenesis and obesity.

  2007cited by this paper
• Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence.

  2007cited by this paper
• Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective

  2007cited by this paper
• Anthropometric measures, plasma adiponectin, and breast cancer risk.

  2007cited by this paper
• Nuclear factor-kappaB in cancer development and progression.

  2006cited by this paper
• Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss

  2006cited by this paper
• Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro.

  2006cited by this paper
• Molecular targets of dietary agents for prevention and therapy of cancer.

  2006influential reference
• Insulin and insulin resistance.

  2005cited by this paper
• Angiogenic and cell survival functions of Vascular Endothelial Growth Factor (VEGF)

  2005cited by this paper
• Leptin, Insulin-Like Growth Factor-1, and Insulin-Like Growth Factor-2 Are Mitogens in ApcMin/+ but not Apc+/+ Colonic Epithelial Cell Lines

  2005cited by this paper
• Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study.

  2005cited by this paper
• Adiponectin and breast cancer risk.

  2004cited by this paper
• Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.

  2004cited by this paper
• Nutrient sensing and metabolic decisions.

  2004cited by this paper
• Leptin receptor signaling and the regulation of mammalian physiology.

  2004cited by this paper
• Obesity and colon cancer: Does leptin provide a link?

  2004cited by this paper
• Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.

  2003cited by this paper
• Inflammation and cancer

  2002cited by this paper
• Cyclooxygenase-2 in human pathological disease.

  2002cited by this paper
• Leptin and prostate cancer

  2001cited by this paper
• Inflammation and cancer: back to Virchow?

  2001cited by this paper
• Spontaneous Inflammatory Bowel Disease in Multiple Mutant Mouse Lines: Association with Colonization by Helicobacter hepaticus

  1998cited by this paper
• Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.

  1996cited by this paper
• [Inflammation and cancer].

  1974cited by this paper

• A reservation-based clinical trial on inflammatory biomarkers in American Indian/Alaska native cancer patients: Rationale and design of the adaptive prehab approaches in cancer healing and education (APACHE) program.

  2026cites this paper
• The M.I.O.C. (Microbiota, Inflammation, Obesity, Cancer) Network

  2025cites this paper
• Obesity and cancer

  2024cites this paper
• Health Behavior Change Intervention Preferences Expressed by American Indian Cancer Survivors From a Southwest Tribal Community: Semistructured Interview Study

  2024cites this paper
• Fat-enlarged axillary lymph nodes are associated with node-positive breast cancer in obese patients

  2021cites this paper
• Anti-obesity Medications in Cancer Therapy: A Comprehensive Insight.

  2021cites this paper
• Mechanisms of action for the anti-obesogenic activities of phytochemicals.

  2020cites this paper
• Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth

  2020cites this paper
• Modulatory functions of bioactive fruits, vegetables and spices in adipogenesis and angiogenesis

  2019cites this paper
• Molecular Mechanisms of Advanced Prostate Cancer

  2018cites this paper
• Obesity and survival in the neoadjuvant breast cancer setting: role of tumor subtype in an ethnically diverse population

  2017cites this paper
• Lunasin Attenuates Obesity-Associated Metastasis of 4T1 Breast Cancer Cell through Anti-Inflammatory Property

  2016cites this paper
• Aspirin Breaks the Crosstalk between 3T3-L1 Adipocytes and 4T1 Breast Cancer Cells by Regulating Cytokine Production

  2016influential citation
• Obesity and cancer: mechanistic insights from transdisciplinary studies.

  2015cites this paper
• Linking Obesity, Metabolism, and Cancer

  2015cites this paper
• The relationship between obesity and cancer

  2015cites this paper
• Novel antitumor mechanisms of curcumin: implication of altered tumor metabolism, reconstituted tumor microenvironment and augmented myelopoiesis

  2014cites this paper
• Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function.

  2014cites this paper
• Obesity: Is it an Independent Risk Factor for Diabetes and Cancer?

  2014cites this paper
• Ellagic Acid Normalizes Mitochondrial Outer Membrane Permeabilization and Attenuates Inflammation-Mediated Cell Proliferation in Experimental Liver Cancer

  2014cites this paper
• Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth.

  2014cites this paper
• The big problem: battling companion animal obesity

  2013cites this paper