{"entity":{"id":"idea-bio2-hypoxia-guided-adenosine","kind":"idea","name":"Use a hypoxia scan to pick patients for adenosine-pathway drugs","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"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)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["rcc","nsclc","prostate"],"sections":[],"technologies":["pet","checkpoint-inhibitor","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-hypoxia-guided-adenosine/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"pet","kind":"technology","name":"PET (positron emission tomography)","route":"/technologies/pet/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"pathway":[{"id":"hif-vhl","kind":"pathway","name":"VHL / HIF oxygen sensing","route":"/pathways/hif-vhl/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}