# An open atlas of collateral sensitivity for every approved targeted drug

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

## TL;DR

When a tumour evolves resistance to one drug, it sometimes becomes weaker against another. Map these trade-offs systematically so doctors can pick the next drug to exploit them.

## Summary

Collateral sensitivity is well characterised in antibiotics and shown in a few oncology examples (MEK-inhibitor resistance sensitising to certain agents, ABL inhibitor rotation in CML). A systematic programme would evolve resistance to each approved targeted agent in dozens of models, screen the resistant derivatives against the full pharmacopoeia, and publish a public sensitivity map to inform sequencing trials.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: For most approved targeted agents, at least one collateral sensitivity with a greater than three-fold shift will be reproducible across models and will translate into a sequencing rule that prolongs second-line response in a trial.
- Rationale: Resistance carries costs. Antibiotic collateral sensitivity maps have already guided cycling regimens; oncology has the models and drugs but has never done the systematic screen.
- Proposed test: Two-year screen across 20 drugs and 200 models with independent replication of top hits; then a randomised second-line sequencing trial in the setting with the strongest signal.
- 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/), [Functional (ex vivo) drug testing](https://onco.cc/technologies/functional-drug-testing/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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