OnCo
ideasIdea

Label every targetable mutation as truncal or branch on the report

A drug aimed at a mutation present in every tumour cell works differently from one aimed at a mutation in only some cells. Test reports should say which is which.

Tumour sequencing reports list alterations without their cancer cell fraction. Adding a clonality estimate (truncal, subclonal with estimated fraction, indeterminate) is computationally routine from purity- and copy-number-adjusted VAFs. Trials could then stratify by clonality and drug labels could state that benefit was shown for clonal alterations.

Hypothesis
Patients whose targetable alteration is subclonal have materially shorter progression-free survival on the matched drug than those with a clonal alteration, and reporting clonality shifts prescribing toward combinations in the subclonal group.
Rationale
Subclonal targets predict poor responses in lung, colorectal and breast cohorts; the field ignores this because reports do not surface it. It costs nothing to compute.
What would test it
Re-analyse the sequencing from three completed targeted-therapy trials to estimate the clonal versus subclonal hazard ratio; if confirmed, pilot clonality labelling with two commercial panel providers and audit prescribing changes.
Maturity
preclinical evidence
Who has to act
data
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks

Connected

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Pages like this

not linked directly; found by shared links

technologies

1
Comprehensive genomic profiling

companies

3
Foundation Medicine (Roche)Guardant HealthTempus AI

terms

2
Next-generation sequencing (NGS)Variant allele frequency (VAF)

bottlenecks

2
Biomarkers are not validated or standardisedTumour heterogeneity and clonal evolution