Towards Better Understanding of the Complex Obesity Cancer Link Obesity and cancer
Main Article Content
Abstract
Obesity is presently one of the major health concerns worldwide, associated with multiple metabolic abnormalities and cardiometabolic diseases. Obesity is also playing a significant role in cancer development and pathogenesis, affecting not only health and quality of life of cancer patients, but also mortality. Additionally, it is a social and economic burden in developed and in developing countries. The potential biological mechanisms linking obesity to cancer development, progression and mortality are not well understood and are still a big challenge. Therefore, the aim of this paper is to clarify some underlying pathological mechanisms linking obesity and cancer, including energy imbalance, insulin resistance, and chronic inflammation. The role of inositol, inositol phosphates and inositol compounds against both obesity and cancer are highlighted in this report. Better understanding of the mechanisms involved in the complex obesity-cancer link is needed, not only to prevent both diseases and to propose dietary strategies and interventions for effective weight management, but also for developing potential therapeutics and pharmacological agents targeting weight loss.
Keywords:
Obesity, cancer, mechanisms, inositol compounds, prevention, interventions
Article Details
How to Cite
VUCENIK, Ivana.
Towards Better Understanding of the Complex Obesity Cancer Link.
Medical Research Archives, [S.l.], v. 13, n. 12, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7149>. Date accessed: 23 jan. 2026.
doi: https://doi.org/10.18103/mra.v13i12.7149.
Keywords
obesity, cancer, mechanisms, inositol compounds, prevention, interventions
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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37. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023; 389:2221-32.
38. Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecifiesd analysis of the SELECT trial. Lancet 2024;404:773-86.
39. Wang L, Xu R, Kaelber DC, et al. Glucagon-like peptide 1 receptor agaonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Netw Open 2024 Jul 1;7(7):e2421305. doi:10.1001/jamanetworkopen.2024.21305.
40. https://clinicaltrials.gov/study/NCT04780477
41. Chatree S, Thongmaen N, Tantivejkul K, et al. Role of inositol and inositol phosphates in energy metabolism. Molecules 2020;25(21):5079.
42. Lentini G, Querqui A, Giuliani A, et al. Inositol and PIP2/PIP3 Ratio: At the Crossroad of the Biodynamic Interface Between Cells and Their Microenvironment. Biomolecules 2025;15(3):451.
43. Dilworth L, Stennett D, Omoruyi F. Cellular and Molecular Activitiesof IP6 in Disease Prevention and Therapy. Biomolecules 2023;13(6):972.
44. Vucenik I, Shamsuddin AM. Protection against cancer by IP6 and inositol. Nutr Cancer 2026;55(2):109.
45. Bizzarri M, Dinicola S, Cucina A. Modulation of both insulin resistance and cancer growth by inositol. Curr Pharm Des 2017;23(34):5200-5210.
46. Sobhanifar A, Arefhosseini S, Tutunchi H, et al. Effects of inositols on adipokines: A systematic review of current knowledge and potential mechanisms. J Functional Foods 2024 March;114;106056
47. Arefhosseini S, Roshanravan N, Tutunchi H, et al. Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease. Front Nutr 2023; Feb 7:10.
48. Perichart-Perera O, Reyes-Muñoz E, Borboa-Olivares H, et al. Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment. Front Med 2024 Apr 12;11:1339428.
49. Mukherjee S, Chakraborty M, Haubner J, et al. The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling. Biomolecules 2023, 13(5), 868.
50. Zhou Y, Mukherjee S, Huang D, et al. Development of Novel Inhibitors for the treatment of Obesity and Obesity-Induced Metabolic Dysfunctions. J Med Chem. 2022 May 12; 65(9):6869-6887.
51. Mondal I, Halder AK, Pattanayak N, et al. Shaping the Future of Obesity treatment: In Silico Multi-Modeling of IP6K1 Inhibitors for Obesity and Metabolic Dysfunction. Pharmaceuticals (Basel). 2024, 17(2):263.
52. Chakraborty A, Koldobskiy MA, Bello NT, et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell. 2010, 143: 897-910.
53. Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 March;31:951-962.
54. Tan HL, Yin L, Tan Y, et al. Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake. Nature 2024;636:198-205.
55. McGowan B, Ciudin A, Baker JL, et al: Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO). Nat Med. 2025 Oct;31(10):3229-3232.
2. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2023/. Accessed October 20, 2025.
3. Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C et al. Projected U.S. State-level prevalence of adult obesity and severe obesity. N Engl J Med 2019;381:2440-2450.
4. Lingvay I, Cohen RV, Roux CWL et al. Obesity in adults. Lancet 2024 Sep 7; 404(10456):972-987.
5. https://www.cdc.gov/obesity/basics/adult-defining.html/. Assessed October 20, 2025.
6. Friedenreich CM, Ryder-Burbidge C, McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biological mechanisms. Mol Oncol 2021; 15:790-800.
7. Moscogiuri G, Barrea L, Bettini S, et al. European Association for the Study of Obesity (EASO) Position Statement on medical nutrition therapy for the management of individuals with overweight or obesity and cancer. Obesity Facts 2024; October 30:1-37.
8. Travellin E, Bettini S, Pilatone A, et al. Obesity, the adipose organ and cancer in humans: Association or causation? Biomedicines 2023; 11(5).
9. World Cancer Research Fund/American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR.
10. https://www.wcrf.org/policy/our-publications/. Assessed October 20, 2025.
11. 2018 Physical Activity Guidelines Advisory Committee (2018) 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Department of Health and Human Services, Washington, DC.
12. Harris BHL, Macaulay VM, Harris DA, Klenerman P, Karpe F, Lord SR et al. Obesity: a perfect storm for carcinogenesis. Cancer Metastasis Rev 2022;41:491-515.
13. I Vucenik I, Jones LP, McLenithan .JC. (2023) Linking Obesity, Metabolism, and Cancer. In: Ahima, RS (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-12125-3_50-2
14. Louie SM, Roberts LS, Nomura DK. Mechanisms linking obesity and cancer. BBA 2013;1831:1499-1508.
15. Ungefroren H, Gieseler F, Fliedner S, Leh H. Adiposopathy in cancer and (cardio)metabolic diseases: an endocrine approach. Horm Mol Clin Invest 2015;21:17-41.
16. Multhoff G, Molls M, Radons J. Chronic inflammation in cancer development. Front Immunol 2012; 2:98.
17. Headland SE, Norling LV. The resolution of inflammation: Principles and challenges. Semin Immunol 2015;27:149-160.
18. Ràfols ME. Adipose tissue: Cell heterogeneity and functional diversity. Endocrinol Nutr 2014; 61:100-112.
19. Stone TW, McPherson M, Darlington LG. Obesity and Cancer: Existing and New Hypotheses for a causal connection. EBioMedicine 2018;30:14-28.
20. Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins. Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis 2010;31:83-89.
21. Friedman JM, Mantzoros CS. 20 years of leptin: From the discovery of leptin gene to leptin in our therapeutic armamentarium. Metabolism 2015;64:1-4.
22. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev 2012;33:547-594.
23. Rock CL, Thomson C, Gansler T, Gapstur SM, McCullough ML, Patel AV et al. American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention. CA Cancer J Clin 2020;70:245-271.
24. Ford NA, Lashinger LM, Allott EH, Hursting SD. Mechanistic targets and phytochemical strategies for breaking the obesity-cancer link. Front Oncol. 2013;3:209.
25. Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann NY Acad Sci 2012;1271:37-43.
26. Kim JN, Han SN, Kim HK. Phytic acid and myo-inositol support adipocyte differentiation and improve insulin sensitivity in 3T3-L1 cells. Nutr Res 2014;34:723-731.
27. Ostan R, Lanzarini C, Pini E, Scruti M, Vianello D, Bertarelli C et al. Inflammaging and cancer: A challenge for the Mediterranean Diet. Nutrients 2015;7:2589-2621.
28. Chlebowski RT, Blackburn GL, Thompson CA, Nixon DW, Shapiro A, Hoy MK et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Woman’s Intervention Nutrition Study. J Natl Cancer Inst 2006;98:1767-1776.
29. Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA 2007;298:289-298.
30. Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt JA et al. The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomarkers Prev 2012;21:1244-1259.
31. Demark-Wahnefried W, Clipp EC, Lipkus IM, Lobach D, Snyder DC, Sloane R et al. Main outcomes of the FRESH START trial: a sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors. J Clin Oncol 2007;25:2709-2718.
32. Rock CL, Byers TE, Colditz GA, Demark-Wahnefried W, Ganz PA, Wolin KY et al. Reducing breast cancer recurrence with weight loss, a vanguard trial: the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial. Contemp Clin Trials 2013;34:282-295.
33. Rock CL, Flatt SW, Byers TE, et al. Results of the Energy and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A behavioral weight loss intervention in overweight or obese cancer survivors. J Clin Oncol 2015 Oct 1;33(28):3169-76.
34. Weber DD, Aminzadeh-Gohari S, Tulipan J, et al. Ketogenic diet in the treatment of cancer – Where do we stand? Mol Metab 2020;33:102-21.
35. Clifton KK, Ma CX, Fontana L, et al. Intermittent fasting in the prevention and treatment of cancer.CA Cancer J Clin 2021; 71(6):527-46.
36. Ryan DH, Lingvay I, Colhoun HM, et al. Semaglutide effects on cardiovascular outcomes in people with overweight and obesity (SELECT) rationale and design. Am Heart J 2020;229:61-69.
37. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023; 389:2221-32.
38. Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecifiesd analysis of the SELECT trial. Lancet 2024;404:773-86.
39. Wang L, Xu R, Kaelber DC, et al. Glucagon-like peptide 1 receptor agaonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Netw Open 2024 Jul 1;7(7):e2421305. doi:10.1001/jamanetworkopen.2024.21305.
40. https://clinicaltrials.gov/study/NCT04780477
41. Chatree S, Thongmaen N, Tantivejkul K, et al. Role of inositol and inositol phosphates in energy metabolism. Molecules 2020;25(21):5079.
42. Lentini G, Querqui A, Giuliani A, et al. Inositol and PIP2/PIP3 Ratio: At the Crossroad of the Biodynamic Interface Between Cells and Their Microenvironment. Biomolecules 2025;15(3):451.
43. Dilworth L, Stennett D, Omoruyi F. Cellular and Molecular Activitiesof IP6 in Disease Prevention and Therapy. Biomolecules 2023;13(6):972.
44. Vucenik I, Shamsuddin AM. Protection against cancer by IP6 and inositol. Nutr Cancer 2026;55(2):109.
45. Bizzarri M, Dinicola S, Cucina A. Modulation of both insulin resistance and cancer growth by inositol. Curr Pharm Des 2017;23(34):5200-5210.
46. Sobhanifar A, Arefhosseini S, Tutunchi H, et al. Effects of inositols on adipokines: A systematic review of current knowledge and potential mechanisms. J Functional Foods 2024 March;114;106056
47. Arefhosseini S, Roshanravan N, Tutunchi H, et al. Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease. Front Nutr 2023; Feb 7:10.
48. Perichart-Perera O, Reyes-Muñoz E, Borboa-Olivares H, et al. Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment. Front Med 2024 Apr 12;11:1339428.
49. Mukherjee S, Chakraborty M, Haubner J, et al. The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling. Biomolecules 2023, 13(5), 868.
50. Zhou Y, Mukherjee S, Huang D, et al. Development of Novel Inhibitors for the treatment of Obesity and Obesity-Induced Metabolic Dysfunctions. J Med Chem. 2022 May 12; 65(9):6869-6887.
51. Mondal I, Halder AK, Pattanayak N, et al. Shaping the Future of Obesity treatment: In Silico Multi-Modeling of IP6K1 Inhibitors for Obesity and Metabolic Dysfunction. Pharmaceuticals (Basel). 2024, 17(2):263.
52. Chakraborty A, Koldobskiy MA, Bello NT, et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell. 2010, 143: 897-910.
53. Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med. 2025 March;31:951-962.
54. Tan HL, Yin L, Tan Y, et al. Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake. Nature 2024;636:198-205.
55. McGowan B, Ciudin A, Baker JL, et al: Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO). Nat Med. 2025 Oct;31(10):3229-3232.