Hyperbaric Oxygen-facilitated Cancer Treatment: Minireview

Can Hyperbaric Oxygen Therapy Improve Cancer Treatment?

Partly. This 2024 minireview of published research argues that hyperbaric oxygen therapy can enhance other cancer treatments by relieving tumor hypoxia, but the clinical trial results it collects are mixed. In the review’s table of trials, breast cancer treated with chemotherapy, esophageal carcinoma treated with radiotherapy, and advanced cancer of the upper gastrointestinal tract treated with photodynamic therapy were graded significantly effective. Several other cancers were graded merely effective, and carcinoma of the cervix was graded not effective.

This is a narrative minireview, not a new trial. The authors summarize other people’s work, and much of what they summarize is animal and nanomedicine research rather than human studies.

Tumors often have very low oxygen levels inside them. This low-oxygen environment, called hypoxia, helps cancer cells survive, resist treatment, and spread. Hyperbaric oxygen therapy has patients breathe pure oxygen at more than one atmosphere of pressure, which raises the amount of oxygen dissolved in plasma. Because that oxygen travels in plasma rather than bound to hemoglobin, it can diffuse into places red blood cells cannot reach, including deep tumor tissue.

What the Data Show

Clinical trials, graded significantly effective: breast cancer with chemotherapy, esophageal carcinoma with radiotherapy, and advanced cancer of the upper gastrointestinal tract with photodynamic therapy
Clinical trials, graded effective: advanced gastric cancer with chemotherapy, advanced squamous cell carcinoma of the head and neck with radiotherapy, lung cancer and advanced malignant bronchial tumor with photodynamic therapy
Clinical trials, graded not effective: carcinoma of the cervix with radiotherapy. Surgery for hepatocellular carcinoma was graded effective but not significant
Tumor penetration: HBO combined with Doxil reached 1.73 times the penetration depth of Doxil alone and 2.87 times that of plain doxorubicin
Collagen reduction: after HBO, tumor fibril content fell by 44%, with CTGF down about 73% and collagen I down about 95%
Glioma model: HBO plus temozolomide-loaded porous silicon nanoparticles produced an 84.2% tumor suppression rate

Dr. Kumar’s Take

This review makes a coherent mechanistic case: hypoxia protects tumors, hyperbaric oxygen relieves hypoxia, and relieving hypoxia should make chemotherapy, radiation, and light-based therapy work better. The proposed pathways go beyond simple oxygen delivery. In the Doxil work the authors describe, HBO also appeared to reduce the collagen deposition that walls a tumor off from circulating drug, which is a different and more interesting mechanism than oxygenation alone.

I would be careful about how the clinical evidence gets summarized. The review’s own table is not a clean win. Cervical carcinoma showed no benefit, hepatocellular carcinoma surgery showed a benefit that did not reach significance, and most of the striking percentages in this paper come from mouse and nanoparticle experiments rather than patients. There is also a real safety caveat: combining HBO with conventional drugs that kill cells by generating reactive oxygen species, doxorubicin among them, has been treated as a contraindication. That is a reason for caution, not enthusiasm, outside a trial.

How HBO Helps Fight Cancer

Tumors develop low-oxygen regions because their blood vessels are structurally and functionally abnormal and because rapidly dividing cells consume more oxygen than the supply can meet. According to the review, this hypoxia causes several problems:

It drives expression of hypoxia-inducible factor-1α, which contributes to multidrug resistance, upregulated autophagy, and inhibited apoptosis
It reduces the effect of radiotherapy, chemotherapy, and photodynamic therapy
It is linked with tumor progression, invasion, and metastasis
Through the HIF-1α pathway, it promotes collagen deposition that can block drug delivery

HBO raises dissolved oxygen in tissue according to Henry’s law, and the authors argue this is simpler and easier to deploy clinically than oxygen carriers or in-situ oxygen-generating chemistry, most of which remain preclinical.

Key Findings Across Treatment Types

Chemotherapy Enhancement: When HBO was combined with Doxil, a liposomal form of doxorubicin, tumor fibril content dropped by 44%, CTGF fell about 73%, and collagen I fell about 95%. Drug penetration depth was 1.73 times that of Doxil alone and 2.87 times that of plain doxorubicin, and tumoral drug accumulation rose accordingly. Markers of liver and kidney function did not differ from control, and serum creatine phosphokinase, an index of heart muscle damage, was significantly lower with Doxil plus HBO than with plain doxorubicin plus HBO.

Nanomedicine in Glioma: HBO combined with temozolomide-loaded porous silicon nanoparticles produced an 84.2% tumor suppression rate in a glioma model, with a lower tumor cell proliferation rate than the nanoparticles alone. After HBO, hypoxia was relieved and more cells were arrested in the G2/M phase, which the authors propose as the mechanism.

Heat Plus Chemotherapy: In one study, the group treated with HBO, mild hyperthermia, and carboplatin showed markedly delayed tumor growth compared with the group treated with mild hyperthermia and carboplatin.

Light Therapy: In a trial of 52 patients with advanced cancer of the upper gastrointestinal tract, combining photodynamic therapy with HBO reduced tumor size significantly and increased mean survival time.

Radiotherapy: In 45 patients with advanced esophageal cancer, adding HBO to an iodine-125 particle-integrated covered esophageal stent produced a noticeably higher total effective rate than the stent without HBO.

Important Limitations

Many of the dramatic percentages in this review come from animal and nanoparticle studies rather than from patients. The clinical results are uneven, including one radiotherapy trial in cervical carcinoma graded not effective.

There is also a drug interaction concern. HBO may worsen the side effects of conventional drugs that work by producing reactive oxygen species, such as doxorubicin, and that combination has been regarded as a contraindication. The liposomal formulation appears to sidestep this in the study described, but that is a single line of work.

The review authors state that challenges remain before HBO enters routine clinical use for cancer, and they frame their paper as a reference for future clinical research rather than a recommendation.

Practical Takeaways

HBO is an approved adjuvant therapy, cleared by the FDA and the Undersea and Hyperbaric Medical Society, and is already used for conditions such as necrotizing soft-tissue infections and carbon monoxide poisoning
Benefit in cancer trials varies by cancer type and by the treatment HBO is paired with, and at least one trial showed no benefit
The proposed mechanisms include oxygen delivery into hypoxic tissue, reduced collagen deposition around tumors, and improved drug penetration
Combining HBO with conventional doxorubicin has been treated as a contraindication because of amplified reactive-oxygen side effects
Talk to your oncologist before considering HBO alongside cancer treatment. It is an adjunct under study, not a replacement for standard therapy

FAQs

How does HBO improve chemotherapy effectiveness?

Hypoxia drives drug resistance, so raising tumor oxygen is expected to reduce it. In the Doxil work described in this review, HBO also reduced the collagen deposited around the tumor by interrupting the HIF-1α, CTGF, collagen I pathway, and drug penetration depth reached 1.73 times that of Doxil alone. In a glioma model, HBO plus temozolomide-loaded nanoparticles gave an 84.2% tumor suppression rate.

Is HBO a cancer treatment on its own?

No. HBO is an adjuvant therapy, meaning it is used to help other treatments work better. It is an approved adjuvant therapy and is used clinically for conditions including necrotizing soft-tissue infections and carbon monoxide poisoning. In cancer it is being studied alongside chemotherapy, radiotherapy, and photodynamic therapy, not in place of them.

What cancers showed the most benefit from HBO in clinical trials?

In the review’s table, the trials graded significantly effective were breast cancer with chemotherapy, esophageal carcinoma with radiotherapy, and advanced cancer of the upper gastrointestinal tract with photodynamic therapy. Advanced gastric cancer, head and neck squamous cell carcinoma, lung cancer, and advanced malignant bronchial tumor were graded effective. Carcinoma of the cervix was graded not effective.

Are there risks to combining HBO with cancer treatment?

Yes. HBO may amplify the side effects of drugs that act by producing reactive oxygen species, doxorubicin among them, and that pairing has been regarded as a contraindication. With the liposomal formulation Doxil, serum creatine phosphokinase was significantly lower than with plain doxorubicin plus HBO, and liver and kidney markers matched control. Discuss HBO with your oncologist before adding it to any treatment plan.

Bottom Line

This 2024 minireview argues that hyperbaric oxygen therapy is a practical way to relieve tumor hypoxia and, through that, to improve chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy. The human evidence it collects is mixed: significant benefit in breast cancer with chemotherapy, esophageal carcinoma with radiotherapy, and upper gastrointestinal cancer with photodynamic therapy, weaker or absent benefit elsewhere, including a cervical carcinoma trial graded not effective. The largest effects, including 1.73 times deeper drug penetration with Doxil, a 44% drop in tumor fibril content, and an 84.2% tumor suppression rate with temozolomide-loaded nanoparticles, come from laboratory and animal work. The authors themselves position HBO as a promising adjuvant that still needs clinical research before routine use.

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