Epigenetic noise fuels cancer evolution

Deep genomic sequencing technologies are beginning to resolve the underlying complexities of solid and hematologic cancers. Peter Nowell’s proposed model for cancer evolution suggesting that cancers evolve through branched evolutionary trajectories fuelled by genomic instability is now increasingly being accepted as a basis for therapeutic failure and the increasing mismatch between cost and clinical benefit from current targeted therapeutic approaches (Nowell, 1976) As Nowell predicted in 1976, “One may ultimately have to consider each advanced malignancy as an individual therapeutic problem.”