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Whole regions of tissue carry cancer mutations long before a tumour exists. Detecting and treating the field, not the tumour, could prevent cancers rather than cure them.
This idea proposes intercepting cancer at the field stage: tissue regions carry cancer mutations long before a tumour exists, so treating the field could prevent cancers rather than cure them. Mutant clones in normal oesophagus, skin and airway are pervasive, and Barrett's ablation, HPV vaccination and Lynch aspirin already show interception works when the field is identifiable (Field cancerisation pathway). The hypothesis is that field markers such as TP53-mutant clone burden in Barrett's oesophagus or bronchial brushings identify people for whom ablation or chemoprevention cuts cancer incidence. The test is a randomised trial of marker-guided ablation against surveillance in non-dysplastic Barrett's, relevant to Oesophageal cancer and Non-small-cell lung cancer.
Carrying a cancer mutation is normal; most mutant clones never become cancer. This means blood or tissue tests that look for driver mutations alone will produce false positives, and that the question of what tips a mutant clone into cancer (tissue environment, further hits, immune surveillance) is as important as the mutation itself.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, The Francis Crick Institute, TP53 and the tags mechanism, open-question.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, TP53 and the tags mechanism, open-question.
Shares Clonal evolution & minimal residual disease, Cancer Research UK and the tags mechanism, open-question.
Shares Clonal evolution & minimal residual disease, Non-small-cell lung cancer and the tags mechanism, open-question.
Shares Head and neck squamous cell carcinoma and the tags mechanism, open-question.
Shares Non-small-cell lung cancer and the tags mechanism, open-question.
Shares Non-small-cell lung cancer and the tags mechanism, open-question.
Shares Non-small-cell lung cancer and the tags mechanism, open-question.