{"entity":{"id":"idea-bio1-evolvability-index","kind":"idea","name":"A standard evolvability score for every tumour","aka":[],"tldr":"Some tumours change fast and escape drugs quickly; others are stable. A single validated score for how evolvable a tumour is would tell doctors how aggressively to combine treatments.","summary":"Copy-number heterogeneity, whole-genome doubling, chromosomal instability signatures, APOBEC activity and ctDNA turnover each predict evolution and relapse in separate studies. The proposal is to define, freeze and prospectively validate one composite evolvability index computed from routine sequencing, analogous to how tumour mutational burden was standardised.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mutational-signature","tmb"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An evolvability index in the top quartile predicts shorter duration of response to single-agent targeted therapy across tumour types, and randomising high-index patients to upfront combinations improves progression-free survival.","rationale":"TRACERx subclonal copy-number heterogeneity predicts recurrence; chromosomal instability scores predict metastasis; measures of evolvability are more general than any single mutation and could guide intensity of therapy.","test":"Consortium defines the index on existing multi-region cohorts, locks it, and validates on three independent trial datasets; then a randomised trial of monotherapy versus combination stratified by index.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-evolvability-index/","neighbours":{"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"term":[{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}