ideasIdea
Use a hypoxia scan to pick patients for adenosine-pathway drugs
Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.
Hypoxia drives CD73-mediated adenosine production and A2A receptor signalling that suppresses T cells and natural killer cells. Adenosine-axis drugs have given inconsistent phase 2 results in unselected populations. Hypoxia PET tracers and validated hypoxia gene signatures could select the patients whose tumours actually run this pathway.
Hypothesis
Adenosine-axis blockade improves response only in patients whose tumours are hypoxia-high by imaging or signature, and pooling hypoxia-low patients accounts for previous inconsistent results.
Rationale
Adenosine generation is mechanistically downstream of hypoxia, so a hypoxia biomarker is causally, not merely statistically, linked to drug relevance. Hypoxia imaging and signatures are mature research tools ready for prospective use.
What would test it
Retrospective interaction analysis of hypoxia signatures in completed adenosine-axis trials; if the interaction holds, run a prospectively hypoxia-selected randomised phase 2.
Maturity
early clinical
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks
- Cold tumours and the immunosuppressive microenvironment · Most tumours keep the immune system out or asleep, so immunotherapy helps only a minority.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.