Cancer isn’t just a cluster of rogue cells, it’s a dynamic and evolving environment. Within that environment, oxygen plays a powerful and often underestimated role. Emerging research suggests that therapies that boost oxygen levels, such as Exercise With Oxygen Therapy (EWOT), may help to weaken tumors and strengthen the body’s own defense systems.

In this article, we’ll explore how oxygen affects the tumor microenvironment, how it lowers harmful factors like VEGF and HIF-1, and why increasing oxygen through EWOT could be a supportive tool in cancer care.

Understanding the Tumor Microenvironment

Cancer cells don’t grow in isolation. They interact with and manipulate their surroundings—blood vessels, immune cells, connective tissue, and signaling molecules—to create a supportive habitat called the tumor microenvironment (TME).

One of the defining characteristics of the TME is hypoxia—a lack of oxygen. As tumors grow rapidly, they often outpace their blood supply, leaving areas within the tumor starved for oxygen. This low-oxygen environment isn’t just a side effect; it actually helps tumors thrive.

Why Hypoxia Fuels Cancer

When oxygen levels drop, cancer cells activate survival mechanisms. Two of the most important players in this hypoxic response are:

1. HIF-1 (Hypoxia-Inducible Factor 1)

HIF-1 is a transcription factor that becomes stabilized in low oxygen conditions. Once active, HIF-1 turns on genes that help cancer cells survive and spread, including those that:

• Promote angiogenesis (new blood vessel growth)
• Increase glucose metabolism (a hallmark of cancer)
• Suppress immune detection

2. VEGF (Vascular Endothelial Growth Factor)

HIF-1 directly stimulates VEGF, a key driver of blood vessel formation. While new vessels might sound good, tumor blood vessels are often leaky and disorganized, worsening hypoxia and making it harder for chemotherapy or immune cells to reach the tumor.

In short: hypoxia → HIF-1 activation → VEGF upregulation → chaotic tumor growth and immune evasion.

How Oxygen Can Turn the Tables

By increasing oxygen availability in the tumor microenvironment, we can disrupt this vicious cycle.

Oxygen downregulates HIF-1

Oxygen is a natural suppressor of HIF-1. In well-oxygenated conditions, HIF-1 is rapidly degraded and cannot trigger the cascade of genes that protect the tumor.

Oxygen reduces VEGF expression

With lower HIF-1 activity, the production of VEGF also drops. This can help “normalize” the tumor vasculature, improving blood flow, reducing metastasis, and enhancing the delivery of therapies.

Oxygen supports the immune response

Immune cells, especially cytotoxic T-cells and natural killer (NK) cells, require oxygen to function optimally. In a hypoxic environment, their ability to recognize and destroy cancer cells is impaired. Oxygen-rich conditions help restore immune surveillance and anti-tumor activity.

What is EWOT? (Exercise With Oxygen Therapy)

EWOT combines moderate exercise (usually on a bike or treadmill) with the inhalation of high-concentration oxygen, typically delivered through a mask hooked up to an oxygen concentrator or reservoir.

The combination of movement and high flow rate oxygen consumption creates a synergistic effect:

• Exercise increases heart rate and blood flow
• Oxygen is more effectively delivered to tissues, including poorly perfused areas
• Over time, EWOT may improve microcirculation and oxygen utilization at the cellular level

This method has been used for decades in sports performance and chronic disease management, but it’s now gaining attention in integrative oncology settings.

Potential Benefits of EWOT in Cancer Care

While EWOT is not a standalone treatment for cancer, it may offer adjunctive support by:

• Improving tissue oxygenation, especially in areas with poor blood supply
• Lowering HIF-1 and VEGF expression, disrupting tumor growth signals
• Enhancing immune function, helping the body mount a stronger anti-cancer response
• Boosting mitochondrial function, which may improve energy metabolism and recovery
• Enhancing effectiveness of therapies, such as radiation and some forms of chemotherapy, which depend on oxygen for maximum efficacy

A Word of Caution

While the science behind oxygen and cancer is compelling, it’s important to note that not all cancers behave the same way, and oxygen therapy is not a cure. Anyone considering EWOT should do so under the guidance of a qualified healthcare provider—preferably one with experience in integrative oncology.

Conclusion: Oxygen as an Ally

The idea that something as simple as oxygen could weaken cancer may seem surprising, but the research is catching up to what many clinicians are already seeing in practice. By targeting the hypoxic tumor microenvironment, therapies like EWOT may help tip the balance in favor of healing.

In the battle against cancer, oxygen isn’t just a passive participant, it’s a powerful ally.

Further Reading / Sources

• Semenza, G.L. (2012). Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends in Pharmacological Sciences.
• Vaupel, P. & Mayer, A. (2007). Hypoxia in cancer: significance and impact on clinical outcome. Cancer and Metastasis Reviews.
• Allen, J. et al. (2018). The role of oxygen in cancer therapy: strategies to overcome hypoxia. Nature Reviews Cancer.