# Goldie-Coldman model of resistance

Source: https://onco.cc/technologies/goldie-coldman-model/  
OnCo record `goldie-coldman-model` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-17
- Tags: mathematical-model
- 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.
- Since: 1979
- 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

## Sources

- Goldie and Coldman 1979, Cancer Treatment Reports (PubMed): https://pubmed.ncbi.nlm.nih.gov/526911/

## Connected records

- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [Evolutionary dynamics of drug resistance](https://onco.cc/technologies/drug-resistance-dynamics/), [Tumour clonal evolution tracking](https://onco.cc/technologies/clonal-evolution-tracking/)

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