| Rank |
Pathway / Axis |
Cancer / Tumor Context |
Normal Tissue Context |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
Tumor hypoxia reduction |
Hypoxia ↓; HIF-1α signaling ↓ (context-dependent) |
Tissue oxygenation ↑ |
P, R |
Microenvironment normalization |
Elevated dissolved oxygen increases tumor pO₂, potentially reducing hypoxia-driven survival programs. |
| 2 |
Radiation sensitization (oxygen fixation effect) |
Radiotherapy efficacy ↑ |
— |
R |
DNA damage amplification |
Oxygen stabilizes radiation-induced DNA radicals, increasing double-strand break lethality. |
| 3 |
ROS generation (hyperoxia-driven) |
ROS ↑ (transient); oxidative stress ↑ |
ROS ↑; antioxidant response ↑ |
P, R |
Redox amplification |
Elevated O₂ increases mitochondrial and enzymatic ROS production; magnitude depends on exposure pressure and duration. |
| 4 |
NRF2 antioxidant response |
Adaptive NRF2 activation ↑ (reported) |
NRF2 ↑; antioxidant enzymes ↑ |
R, G |
Redox adaptation |
Repeated hyperoxic exposure can induce antioxidant defense systems; may influence redox-sensitive therapies. |
| 5 |
HIF-1α / hypoxia signaling modulation |
HIF-1α ↓ (acute hyperoxia); VEGF modulation |
Hypoxia signaling ↓ |
R |
Hypoxia pathway suppression |
Reduced hypoxia may decrease glycolytic shift and angiogenic drive in some tumors. |
| 6 |
Angiogenesis modulation |
VEGF modulation (context-dependent) |
Wound-healing angiogenesis ↑ |
G |
Vascular remodeling |
HBOT stimulates angiogenesis in ischemic tissue; tumor angiogenic response varies by context. |
| 7 |
Immune modulation |
Innate immune activity modulation |
Neutrophil function ↑; inflammation modulation |
R |
Inflammatory modulation |
Hyperoxia can alter cytokine signaling and leukocyte behavior. |
| 8 |
Combination therapy interaction |
May enhance radiotherapy; effects with chemo variable |
— |
R, G |
Adjunctive leverage |
Most consistent evidence supports radiosensitization; chemotherapy interactions are drug-specific. |
| 9 |
Safety constraints |
— |
Oxygen toxicity (CNS/pulmonary); barotrauma risk |
— |
Exposure limitation |
High-pressure or prolonged exposure can cause oxygen toxicity seizures or lung injury. |