# Use a hypoxia scan to pick patients for adenosine-pathway drugs

Source: https://onco.cc/ideas/idea-bio2-hypoxia-guided-adenosine/  
OnCo record `idea-bio2-hypoxia-guided-adenosine` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: industry

## Sources

- Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019): https://doi.org/10.1001/jamanetworkopen.2019.2535

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [PET (positron emission tomography)](https://onco.cc/technologies/pet/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- pathways: [VHL / HIF oxygen sensing](https://onco.cc/pathways/hif-vhl/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs](https://onco.cc/key-papers/paper-haslam-jama-netw-open/)

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