From Gut to Growth Signals: How Obesity Creates a Pro-Cancer Environment

Obesity is often discussed in connection with diabetes, cardiovascular disease, or joint problems. But over the past two decades, research has made another connection increasingly clear: obesity can also influence cancer risk and progression.

Scientists now understand that excess body fat is not simply stored energy. Adipose tissue is an active metabolic organ that produces hormones, immune signals, and growth factors. When present in excess, these signals can reshape the body’s internal environment in ways that support tumor development, which helps explain why obesity is now linked to increased risk of a number of cancers, including postmenopausal breast, colorectal, endometrial, kidney, pancreatic, and esophageal cancers.

Adipose Tissue: More Than Just Fat

In a healthy body, adipose tissue stores energy and helps regulate metabolism. But as adipose tissue expands in obesity, it undergoes structural and functional changes.

Fat cells, or adipocytes, become enlarged beyond their healthy capacity, leading to cellular dysfunction and stress responses (such as low oxygen levels, impaired protein falling, and increased inflammatory signaling). Some eventually die due to sustained cellular stress, releasing signals that trigger an immune response to clear the damaged cells. As macrophages and other immune cells move to clear the cells, they often form crown-like structures, in which macrophages surround dying adipocytes.

Although this is part of a normal biological repair process, persistent adipocyte stress can drive chronic, low-grade inflammation. In turn, inflamed adipose tissue releases elevated levels of signaling molecules such as:

• Tumor necrosis factor-alpha (TNF-α)
• Interleukin-6 (IL-6)
• Chemokines that recruit additional immune cells

These inflammatory signals can circulate throughout the body, contributing to systemic inflammation and metabolic dysfunction. Over time, that inflammatory state can influence how cells grow, divide, and respond to damage.[1]

Why Visceral Fat Matters

Not all body fat behaves in the same way.

Visceral fat, the fat stored deep within the abdomen around internal organs, is especially active in producing inflammatory signals. Compared with subcutaneous fat (fat which sits beneath the skin), visceral fat contains more immune cells and higher levels of inflammatory cytokines.

Because visceral fat lies close to organs such as the colon, pancreas, and liver, it may affect nearby tissues more directly through local signaling. Clinical studies have shown that inflamed adipose tissue in obese individuals is associated with worse outcomes in several cancers, including breast cancer and oral cancers such as tongue cancer. These findings reinforce the principle that fat tissue can actively shape the tumor environment.[1][2]

Hormones From Fat: The Adipokine Shift

Adipose tissue also produces hormones called adipokines, which help regulate metabolism and immune responses.In obesity, the balance of these hormones shifts in ways that may favor cancer development.

Increased Leptin

Leptin levels rise as body fat increases. While leptin normally helps regulate appetite and energy balance, high levels can also influence cancer biology. Leptin has been shown to promote:

• Cancer cell proliferation
• Angiogenesis (the formation of new blood vessels that supply tumors)
• Tumor cell migration and invasion

These effects occur through activation of signaling pathways such as JAK/STAT3, PI3K/AKT, and MAPK, all of which are commonly involved in cancer growth. Leptin can also stimulate aromatase activity (conversion of androgens into estrogens), a mechanism particularly relevant in hormone-sensitive cancers such as breast cancer.[3]

Decreased Adiponectin

At the same time, obesity is associated with lower levels of adiponectin, a hormone with anti-inflammatory and metabolically protective effects.

Adiponectin normally improves insulin sensitivity, activates AMPK signaling, and helps restrain cell proliferation. When adiponectin levels fall, this protective influence is reduced, removing an important brake on tumor-promoting processes.

Other adipokines, including resistin, MCP-1, and macrophage migration inhibitory factor (MIF), may further contribute to inflammation, oxidative stress, and tumor cell survival.[3]

Metabolism, Insulin, and Cancer Growth

Obesity is strongly associated with insulin resistance, a condition in which the body’s cells become less responsive to insulin.

To compensate, the pancreas produces more insulin, resulting in chronic hyperinsulinemia. In turn, elevated insulin levels stimulate the production of insulin-like growth factors, including IGF-1 and IGF-2—molecules that are potent growth signals.

Insulin and IGFs activate pathways such as:

• PI3K/AKT/mTOR
• Ras/Raf/MEK/ERK

These pathways promote cell proliferation, support survival, and reduce programmed cell death. When chronically elevated, they can create favorable conditions for pre-malignant cells to expand and acquire additional mutations.

In effect, the metabolic environment created by obesity continuously sends signals that encourage cells to divide and survive.[3][4]

When the Immune System Struggles to Respond

The immune system plays a crucial role in identifying and eliminating abnormal cells before they become tumors. However, obesity can weaken that protective function.

Chronic inflammation in adipose tissue alters immune cell behavior. Macrophages may shift toward an M2-like phenotype, which supports tissue repair but can also promote tumor growth. Meanwhile, key anti-tumor immune cells become less effective.

For example:

• Natural killer (NK) cells, which normally destroy abnormal cells, may lose some of their cytotoxic ability
• T cells may develop features of exhaustion, reducing their ability to attack malignant cells
• Regulatory T cells and myeloid-derived suppressor cells may increase, further dampening anti-tumor immunity

The combination of persistent inflammation and reduced immune surveillance can allow abnormal cells to survive, adapt, and eventually develop into tumors.[2]

Connecting the Dots

Taken together, obesity influences cancer risk through several interconnected biological mechanisms:

• Chronic inflammation driven by adipose tissue
• Hormonal changes involving adipokines such as leptin and adiponectin
• Metabolic signaling through insulin and IGF pathways
• Impaired immune surveillance

Together, these mechanisms create an internal environment in which cancer cells may find it easier to grow and spread.

The encouraging reality is that many of these pathways are modifiable. Weight management, regular physical activity, and improved metabolic control can reduce inflammation and improve insulin sensitivity. Researchers are also exploring therapies that target these mechanisms directly, including anti-inflammatory approaches, metabolic drugs such as metformin, and agents that influence leptin or IGF signaling.

Understanding the biological connection between obesity and cancer helps shift the conversation away from blame and toward biology, highlighting the importance of prevention, early intervention, and more personalized approaches to care.[2][4]

Reference :

1. Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol. 2016;34(35):4270-4276. doi:10.1200/JCO.2016.67.4283

2. Miracle CE, McCallister CL, Egleton RD, Salisbury TB. Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer. Biochem Biophys Res Commun. 2024;733:150437. doi:10.1016/j.bbrc.2024.150437

3. Bocian-Jastrzębska A, Malczewska-Herman A, Kos-Kudła B. Role of Leptin and Adiponectin in Carcinogenesis. Cancers (Basel). 2023;15(17):4250. Published 2023 Aug 24. doi:10.3390/cancers15174250

4. Pu X, Chen D. Targeting adipokines in obesity-related tumors. Front Oncol. 2021;11:685923. doi:10.3389/fonc.2021.685923

Jacek Antas

Chief Executive Officer

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
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Brenda is the Clinical Operations Director at Helix Biopharma Corp. A clinical research operations professional with 25 years of experience managing clinical trials, ranging from early Phase I to late Phase IIIb/IV studies, she brings experience in clinical study protocol writing and development, trial start-up and vendor management, and a proven track record in planning and managing clinical trials to quality standards, timelines and budget. Brenda joined Helix Biopharma Corp. in 2018, working to advance the clinical program of L-DOS47. She holds B.Sc and M.Sc. degrees from the University of Toronto, specializing in Nutritional Sciences and Human Biology.

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Chairman of the Board

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Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
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Jonathan Davis

Advisor, ADC Discovery

Jonathan Davis received his Ph.D. from University of California, San Francisco, where he studied protein structure and function using NMR. After a post-doc at Harvard Medical School exploring RNA selection and structure in the labs of Jack Szostak and Gerhard Wagner, he went to work at EMD Serono, where his work involved improving antibody-based therapeutics, inventing a platform technology for generating heterodimeric Fcs as a basis for multifunctional molecules, and developing a novel scaffold based on an artificially-designed protein from David Baker’s lab. In 2008 he took a job at Bristol-Myers Squibb in Waltham/Cambridge MA, working on antibody discovery and platform development in a wide range of therapeutic areas, with a particular focus on multispecific therapeutics. He moved to Madison, WI in 2019 to take on the role of VP of Innovation and Strategy at Invenra, a biotech focused on bispecific antibodies, and where he is currently head of the Scientific Advisory Board. In early 2024 he left the corporate world to found Creative Antibodies, a consulting firm that helps guide companies to successful antibody discovery and development projects, from mAbs to multispecifics, ADCs, and other formats. Outside of science, Jonathan is a conservatory trained cellist, plays numerous other instruments, and founded the UCSF Orchestra (now Symphony Parnassus) in San Francisco, where he was Music Director for six years.

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Advisor, CMC

Davide graduated as a pharmacist and received his PhD in Pharmaceutical Technology and Biotechnology from the University of Vienna. He has over 20 years of experience in the pharmaceutical industry, principally in the field of oncology. At the beginning of his career, Davide led oncology business units and commercial departments at Mundipharma and Gilead across Austria and Eastern Europe. Since over 10 years he has been working as a CMC expert, covering operational and regulatory CMC functions on behalf of over 20 different small- and medium-sized biotech companies across the world. He has served as CMC Director and CSO/CTO for several years, developing both small molecules and biologics (mABs, Fab, ADCs and Radio-immuno-conjugates) from early discovery to NDA/BLA in the US, EU and Canada, with a focus on First-in-Human and Phase I/II studies in oncology indications.

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