Response Heterogeneity in Cancer - The Acute Lymphoblastic Leukaemia Paradigm

The first course of treatment often eradicates over 90% of cancer cells. The residual fraction is termed minimal residual disease (MRD). Irrespective of the nature of subsequent therapy, which often leads to molecular disease remission, the burden of MRD after the first course is highly predictive of outcome in many cancers. In childhood acute lymphoblastic leukaemia, we have extensively studied the effect of the genetic heterogeneity, specific targeted therapy and the influence of the microenvironment to understand the complex interactions that promote cell survival and lead to disease recurrence. Understanding the biological basis of MRD offers paradigms for other cancers and presents novel curative strategies.