Cancer Evolution Under Therapy

Drug resistance is a largely unsolved problem in oncology. Despite the explanatory power of the genetic model of cancer initiation, most treatment resistance is unexplained by genetics alone. Even when known resistance mutations are present, they are often found in a small proportion of the cells in the tumour. So where is the cellular memory that leads to treatment failure? New evidence suggests resistance is multi-factorial, resulting from the contribution of heritable genetic and epigenetic changes, but also non-heritable phenotypic plasticity.

We combine dense longitudinal tracking, single cell multi- omics, evolutionary modelling, and archetypal analysis to study how different drugs select for distinct subclones and what are the molecular markers of genetic and non-genetic drug resistance.