Can Pressurized Oxygen Help or Hurt in Cancer? A New Review Says It Depends

Abstract illustration of an oxygen-starved tumor region contrasted with well-oxygenated tissue during hyperbaric exposure

Tumors are, in a blunt physiological sense, oxygen-starved. They outgrow their own blood supply, and the resulting hypoxia drives much of the aggressive biology that makes cancer hard to treat. That fact has kept hyperbaric oxygen therapy (HBOT) circling oncology for decades as both a temptation and a worry: if oxygen-starved tumors are the dangerous ones, does flooding them with pressurized oxygen help — or feed the fire?

A new review published September 3 in Biology (Basel) takes that question head-on and lands somewhere less dramatic, and more useful, than either camp would prefer. Its authors — Turan Demircan and colleagues from Izmir Bakircay University and Mugla Sitki Kocman University in Türkiye — argue that HBOT is best understood not as an anti-cancer weapon or a tumor accelerant, but as a context-dependent modulator of tumor and normal-tissue biology.

The Fear That Would Not Die

Historically, many oncologists treated an active malignancy as a relative contraindication to HBOT, on the theory that raising tissue oxygen tension would stimulate proliferation, angiogenesis or metastasis. The concern was never pure superstition. As the review notes, an early experiment found that tumor cells harvested from the most hypoxic regions of murine solid tumors showed a transient increase in lung-colonizing ability after reoxygenation.

But the authors also point out why the old framing was too simple. Chronic hypoxia stabilizes hypoxia-inducible factors (HIFs) and promotes metabolic reprogramming, angiogenesis, epithelial–mesenchymal transition, cancer stemness, immune suppression and resistance to radiotherapy. In other words, the hypoxic tumor is already the dangerous one. Meanwhile, severe or sustained oxygen limitation can itself constrain tumor expansion — one recent preclinical study found that systemic hypoxia suppressed solid-tumor growth across multiple models by perturbing purine metabolism. Oxygen, in short, is not a switch labeled “grow.”

The review therefore treats HBOT as a transient perturbation rather than a permanent fix: a short, pressure-defined window in which tumor oxygenation, redox balance, vascular tone and immune activity all shift at once. What that shift does depends on baseline hypoxia, tumor phenotype, antioxidant capacity and — critically — timing.

Where the Evidence Is Genuinely Strong

Here the review is unusually clear, and it is not about cancer treatment at all. The strongest clinical support for HBOT in cancer patients concerns late radiation-induced normal-tissue injury, especially radiation cystitis. A scoping review and meta-analysis of 602 patients reported partial or complete resolution of hemorrhagic radiation cystitis in 84 percent of treated patients, with recurrence in 14 percent of those followed. A separate systematic review of 556 patients found symptomatic improvement in roughly 90 percent and complete remission of hematuria in 55 percent. Randomized evidence goes further: the RICH-ART trial and its long-term follow-up showed sustained improvement in patient-reported urinary symptoms, and the treatment was generally well tolerated.

That is a meaningful difference in evidence quality. The case for HBOT in radiation cystitis rests on randomized and pooled clinical data; the case for HBOT as an anti-cancer intervention rests almost entirely on cell and animal work.

The Preclinical Picture Is Genuinely Mixed

The review catalogs how differently tumors respond. Real-time EPR oximetry in B16-F10 melanoma measured tumor oxygen tension rising from roughly 9 mmHg at baseline to about 26 mmHg on normobaric 100% oxygen and to roughly 50 mmHg at 2 ATA, with the effect partially persisting after decompression. A different solid-tumor model exposed to the same conditions barely budged — a reminder that HBOT does not reliably oxygenate every tumor.

Against the growth scare, the record is far from damning. In prostate cancer xenografts (LNCaP and PC-3), repeated HBOT did not produce sustained increases in tumor growth or angiogenic activity, and a latent prostate cancer model showed no acceleration — a point of practical relevance for prostate cancer survivors treated with HBOT for hemorrhagic cystitis. In triple-negative and HER2-positive breast cancer xenografts, HBOT actually suppressed tumor growth, reduced metastatic burden and lowered epithelial–mesenchymal transition markers such as N-cadherin and Axl. It did not, however, improve the effect of 5-fluorouracil, illustrating that reoxygenation and chemotherapy do not automatically cooperate.

The mechanistic case for combining HBOT with radiotherapy — the oxygen fixation hypothesis — remains attractive but unproven at the bedside. Its benefit depends on irradiation coinciding with the reoxygenation window, a scheduling question no trial has resolved.

What Regulators and Specialty Bodies Actually Say

None of this moves HBOT into the cancer-treatment column. HBOT devices are Class II medical devices cleared by the FDA through the 510(k) process under Product Code CBF, and the cleared indications — decompression sickness, carbon monoxide poisoning, non-healing diabetic wounds, late radiation tissue injury, compromised grafts and flaps and others — do not include treating cancer itself. Medicare’s National Coverage Determination 20.29 likewise covers a defined list of established uses. The Undersea and Hyperbaric Medical Society’s indications list includes delayed radiation injury and compromised grafts and flaps, but not oncology.

The FDA has also kept a steady eye on the hardware. Its August 25, 2025 letter to health care providers reminded facilities that the agency is aware of reports of serious injuries and deaths involving HBOT devices, including fires, and urged providers to follow manufacturer instructions, maintain fire-prevention measures, train and monitor staff, and avoid prohibited items in the chamber. That warning stands as the necessary bookend to any enthusiastic account of what pressurized oxygen can do — and it applies with particular force to clinics marketing HBOT for uses that were never cleared.

The Reasonable Middle

The review’s closing position is narrow, and deliberately so. HBOT is not supported as a standalone anti-cancer therapy, and it is not supported as a universal tumor accelerant. Its most defensible role in oncology today is treating the collateral damage of cancer care — radiation cystitis, soft-tissue and bony radiation necrosis — while its future as an adjunct may hinge on whether researchers can measure tumor oxygenation directly, stratify patients by baseline hypoxia and redox phenotype, and schedule treatment precisely enough to exploit a brief reoxygenation window.

For patients, the practical reading is simple enough. If HBOT is being offered to repair radiation injury or to support a cleared diagnosis, it sits on solid ground. If it is being sold as a way to fight the cancer itself, the evidence — and the regulatory record — do not yet go that far.

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