Obesity is not merely an issue of appearance. It is a complex condition that profoundly alters the functioning of the organism, where hormones, metabolism, inflammation, the immune system, and, as widely recognized today by the scientific community, the risk of developing different types of cancer are all affected.
The incidence of obesity has increased in recent years, and it is expected that by 2040 its incidence will rise by 54.9% following current trends, according to Globocan 2020. Currently, the Americas and Europe present prevalence rates of 30% and 25%, respectively, being the highest worldwide.
In a systematic literature review developed by Hernando-Requejo & García de Quinto, solid evidence is presented showing how the state of obesity in individuals acts as an active factor in multiple biological processes that favor the appearance and progression of tumors. Understanding these mechanisms does not aim to create alarm but to offer a powerful tool for prevention and self-care.
Overweight and obesity are defined by an excess of body fat, generally measured using the body mass index (BMI ≥ 25 kg/m² for overweight and ≥ 30 kg/m² for obesity). Its etiology is multifactorial: sedentary lifestyle, overeating, sleep alterations, psychological factors, genetics, medications, pregnancy, alcohol, tobacco, and even socioeconomic environment.
Hanahan and Weinberg described the well-known Hallmarks of Cancer, which are a set of fundamental biological characteristics that explain how normal cells transform into cancer cells and how tumors manage to grow, survive, invade, and spread throughout the body.
Some of the most recognized Hallmarks are: increased cellular proliferation, evasion of growth suppression, resistance to cell death, cellular immortality, angiogenesis, activation of invasion and metastasis, pro-inflammatory state, and immunosuppression. These characteristics are influenced by obesity through different molecular and metabolic mechanisms, as demonstrated by various studies.
Figure 1. Excess adipose tissue alters hormonal, metabolic, and inflammatory signaling, promoting increased proliferation, reduced tumor suppression, impaired apoptosis, telomere dysfunction, abnormal angiogenesis, enhanced invasiveness, and immune exhaustion.
Increased cellular proliferation
For a cell to become cancerous, it must first divide more than normal. In obesity, elevated levels of several hormones and inflammatory molecules function as a “pedal stuck to the floor”, facilitating the emergence of cellular clones with malignant potential.
Adipose tissue produces large amounts of leptin, a hormone that normally regulates appetite but in excess acts as a potent growth factor.
Leptin activates pathways such as JAK/STAT, PI3K/AKT, and MAPK, all associated with proliferation and cell survival. This constant activation creates a state of hyperstimulation in which cells receive signals of “divide and grow” even when unnecessary.
Additionally, increased visceral fat raises estrogen levels, especially through aromatization of androgens in adipose tissue. These estrogens can activate hormone receptors in tissues such as the breast or endometrium, promoting proliferation and increasing the risk of hormone-dependent cancers.
In parallel, excess fat produces insulin resistance, which generates constantly elevated insulin and IGF-1 levels. Both act as mitogens (signals that induce cell division), stimulating entry of cells into the cell cycle.
Finally, inflammation of adipose tissue releases IL-6, a cytokine that activates STAT3, a factor that favors proliferation, survival, and tumor growth.
Evasion of growth suppressors
The body has safety mechanisms designed to prevent dangerous cell divisions. In obesity, several of these brakes weaken or deactivate.
Adiponectin, a protective hormone, decreases significantly in obesity. Adiponectin has anti-inflammatory functions, improves insulin sensitivity, and in the context of cancer, inhibits proliferative pathways. Its reduction removes a key controller of growth.
Additionally, constant inflammation of adipose tissue and metabolic stress alter the functioning of suppressor genes such as p53.
This factor is known as the “guardian of the genome” because it constantly supervises DNA integrity and decides what the cell should do when something goes wrong, whether to repair DNA, slow division, or directly destroy the damaged cell.
When p53 is compromised, DNA damage control weakens, allowing mutated cells to continue dividing.
Other suppressors, such as PTEN and TGF-β, also lose effectiveness in a chronic inflammatory environment favored by obesity. PTEN normally inhibits the PI3K/AKT pathway, and its dysfunction allows excessive proliferation. TGF-β, which regulates growth and differentiation, can switch roles in pro-inflammatory environments and favor tumor development.
Resistance to cell death (anti-apoptosis)
Damaged or dangerous cells should be eliminated through apoptosis, a process that regularly occurs in a normal physiological state. In obesity, several mechanisms block this programmed cell death.
The structural collapse of adipose tissue in obesity (characterized by enlarged adipocytes and low oxygen conditions) activates mediators such as type IV collagen, leptin, and pro-inflammatory cytokines that block apoptotic pathways, allowing damaged cells with mutations or stress to remain alive.
Hypoxia also activates HIF-1α, a factor that promotes cell survival and reprograms metabolism toward more resistant pathways, similar to those used by cancer cells.
Cytokines such as IL-6 and TNF-α, at chronic levels, generate paradoxical signals—initially they may promote cell death, but when the stimulus is continuous, they activate pathways that favor survival and inflammation.
Cellular immortality
“Immortality” does not mean that a cell cannot be destroyed, but rather that it becomes immune to natural mechanisms that limit its lifespan—something like being immune to aging.
Telomeres are structures at the ends of chromosomes that function like a “fuse” determining how many times a cell can divide during its life, with a limit between 40 and 60 divisions, known as the Hayflick limit.
The chronic inflammatory environment generates free radicals, highly reactive molecules that damage DNA. This oxidative stress increases mutation rates.
Obesity is also associated with telomere shortening, the structures that protect chromosome ends. Shorter telomeres mean that cells are under stress and accumulate errors faster.
When abnormal cells manage to activate the telomerase enzyme, they can maintain their telomeres and become “immortal,” a classic hallmark of cancer cells.
Increased angiogenesis (formation of blood vessels)
A growing tumor needs oxygen and nutrients. Obesity facilitates the creation of additional blood vessels that support this expansion. Inflamed adipose tissue produces high levels of VEGF, one of the most important pro-angiogenic factors.
Additionally, hypoxia within adipose tissue increases production of HIF-1α, which in turn activates more VEGF. This network of new vessels not only irrigates adipose tissue but also provides a ready-made route for tumor cells to travel elsewhere (metastasis).
Increased invasion and metastasis
For cancer to become deadly, it must spread to other tissues. Obesity promotes this capacity for movement and colonization. Leptin stimulates cell migration processes, promoting epithelial–mesenchymal transition (EMT), a state that grants tumor cells greater mobility.
Excess insulin activates pathways such as MAPK and AKT, which increase cellular plasticity and facilitate invasion.
Adipocytes near the tumor can transform into cancer-associated adipocytes (CAAs), which release enzymes (such as MMPs) that degrade the extracellular matrix, opening pathways that allow tumor cells to migrate.
Pro-inflammatory state and immunosuppression
Inflammation is one of the most powerful engines of cancer. In obesity, this inflammation is constant and acts in two directions:
Chronic inflammation begins when enlarged adipocytes experience stress and hypoxia, releasing damage signals. This attracts macrophages and immune cells that, instead of resolving the inflammation, become continuous sources of IL-6, TNF-α, and MCP-1.
This leads to increased mutations, promotes proliferation, induces angiogenesis, and reprograms tumor metabolism.
Additionally, this process has a critical side effect: it exhausts T lymphocytes (elite soldiers of the immune response), reduces their activation capacity, and allows malignant cells to go unnoticed.
Thus, the immune system enters a state of “fatigue” where it recognizes less and acts poorly.
The relationship between obesity and cancer is deeper than previously understood. Today we know that adipose tissue acts as an active organ that, when it exceeds its normal capacity, favors several of the key processes of cancer.
This invites us to pursue a healthier lifestyle, not only to look well but to genuinely be well.
Main reference:
Hernando-Requejo, O., & García de Quinto, H. (2024). La obesidad y su relación con el cáncer [Obesity and its relationship with cancer]. Nutricion hospitalaria, 41(Spec No3), 52–56. https://doi.org/10.20960/nh.05459
Other references:
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S., & Dalamaga, M. (2019). Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism: clinical and experimental, 92, 121–135. https://doi.org/10.1016/j.metabol.2018.11.001
Ingram, Y., Olujide, O., Sheikh, N., Robinson, A., Ho, J. H., Syed, A. A., & Adam, S. (2025). The Relationship Between Obesity and Cancer: Epidemiology, Pathophysiology, and the Effect of Obesity Treatment on Cancer. Current oncology (Toronto, Ont.), 32(6), 362. https://doi.org/10.3390/curroncol32060362
Rubino, F., Cummings, D. E., Eckel, R. H., Cohen, R. V., Wilding, J. P. H., Brown, W. A., Stanford, F. C., Batterham, R. L., Farooqi, I. S., Farpour-Lambert, N. J., le Roux, C. W., Sattar, N., Baur, L. A., Morrison, K. M., Misra, A., Kadowaki, T., Tham, K. W., Sumithran, P., Garvey, W. T., Kirwan, J. P., … Mingrone, G. (2025). Definition and diagnostic criteria of clinical obesity. The lancet. Diabetes & endocrinology, 13(3), 221–262. https://doi.org/10.1016/S2213-8587(24)00316-4
