# Barcode patient-derived tumours to watch which clones win under each drug

Source: https://onco.cc/ideas/idea-bio1-barcoded-avatars-clonal-fitness/  
OnCo record `idea-bio1-barcoded-avatars-clonal-fitness` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tag every cell in a patient's lab-grown tumour with a unique DNA label, give it a drug, and read the labels to see which cells survive. This predicts which resistant clone will emerge.

## Summary

Lentiviral cellular barcoding of organoids or PDX models allows quantitative clonal tracking under therapy. Applied to patient avatars before treatment, it would measure the pre-existing resistant clone fraction and fitness under candidate drugs, prioritising combinations that suppress all high-fitness clones rather than the bulk.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Barcoded avatar clonal dynamics predict the dominant resistance clone found in the patient's progression biopsy in most cases, and drug combinations chosen to suppress all barcoded winners extend avatar time-to-regrowth compared with bulk-response-chosen combinations.
- Rationale: Barcoding studies in cell lines and PDX (for example in breast and lung models) show that resistance often arises from rare pre-existing clones whose identity is stable and predictable, not from random de novo events.
- Proposed test: Barcode 30 patient-derived models with matched clinical follow-up, treat with the patient's actual regimen, and compare the barcoded winner genotype with the patient's progression biopsy.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- technologies: [CRISPR functional genomics](https://onco.cc/technologies/crispr-screens/), [Patient-derived organoids](https://onco.cc/technologies/organoids/), [Patient-derived xenografts](https://onco.cc/technologies/pdx-models/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- bottlenecks: [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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