# Clonal evolution and branching models

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

## TL;DR

Peter Nowell's 1976 idea that a tumour is an evolving population of competing clones is now measured directly by sequencing several regions or repeated blood samples, and models of branching evolution predict which clones will drive relapse.

## Summary

Nowell proposed that tumours arise from a single cell and evolve by mutation and selection into a branching tree of clones. Multi-region sequencing (TRACERx in lung cancer, from 2017) and longitudinal circulating tumour DNA confirmed branched evolution, showed truncal versus subclonal mutations, and revealed that some tumours evolve neutrally while others show strong selective sweeps. Models built on these data estimate mutation rates, timing of metastasis and the likelihood that a subclone carries resistance, and inform which mutations to target (truncal) and how to read residual disease.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-17
- Tags: mathematical-model
- Principle: A tumour is a population under mutation, drift and selection; phylogenetic and branching-process models reconstruct its history from the variant allele frequencies observed across regions and time.
- Since: 1976
- Strengths: Directly supported by multi-region and serial sequencing; Distinguishes truncal from subclonal targets; Quantifies intratumour heterogeneity
- Limitations: Sampling misses small clones; Neutral versus selected evolution is debated; Costly to measure in routine care

## Sources

- Nowell 1976, Science: https://doi.org/10.1126/science.959840
- TRACERx, Jamal-Hanjani 2017: https://doi.org/10.1056/NEJMoa1616288

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [Continuous and near-continuous ctDNA monitoring](https://onco.cc/technologies/continuous-ctdna-monitoring/), [Tumour clonal evolution tracking](https://onco.cc/technologies/clonal-evolution-tracking/)

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