{"entity":{"id":"goldie-coldman-model","kind":"technology","name":"Goldie-Coldman model of resistance","aka":[],"tldr":"Resistant cells arise by chance mutation as a tumour grows, so the chance of a cancer already containing resistant cells rises with its size. The model argued for treating early and for alternating non-cross-resistant drugs.","summary":"James Goldie and Andrew Coldman adapted Luria and Delbruck's bacterial mutation analysis to tumours in 1979: resistance to a drug arises spontaneously at a rate per cell division, so the probability that a tumour of a given size harbours resistant cells is a function of its size and the mutation rate. Their conclusions were to start chemotherapy as early as possible and to alternate non-cross-resistant regimens to pre-empt resistance. Alternating schedules largely failed in trials, but the underlying logic survives in modern evolutionary models and in the case for adjuvant therapy of micrometastatic disease.","status":"established","asOf":"2026-09-17","links":[{"label":"Goldie and Coldman 1979, Cancer Treatment Reports (PubMed)","url":"https://pubmed.ncbi.nlm.nih.gov/526911/"}],"tags":["mathematical-model"],"related":[],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["drug-resistance-dynamics","clonal-evolution-tracking"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"principle":"Probability that no resistant cell exists in a tumour of N cells with mutation rate u is about exp(-u·N); resistance is therefore expected once tumours exceed roughly 1/u cells.","strengths":["First quantitative theory of acquired resistance","Justified adjuvant treatment of small tumour burdens","Ancestor of modern evolutionary models"],"limitations":["Alternating regimens did not improve outcomes in trials","Ignores pre-existing and adaptive resistance","Mutation rates poorly known"],"since":1979},"route":"/technologies/goldie-coldman-model/","neighbours":{"section":[{"id":"ai-computation","kind":"section","name":"AI & Computation","route":"/fronts/ai-computation/"},{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}],"technology":[{"id":"drug-resistance-dynamics","kind":"technology","name":"Evolutionary dynamics of drug resistance","route":"/technologies/drug-resistance-dynamics/"},{"id":"clonal-evolution-tracking","kind":"technology","name":"Tumour clonal evolution tracking","route":"/technologies/clonal-evolution-tracking/"}]}}