LAUSR

Simple Summary Breast cancer is a heterogeneous disease that is driven by genetic, epigenetic and phenotypic modifications and is also affected by the microenvironment and the metabolism. In this article we review genetic and non-genetic causes of tumor heterogeneity focusing on the impact that heterogeneity has on resistance to therapy. We will provide examples of personalized medicines and their translation to the clinic. Abstract Targeted cancer therapies against oncogenic drivers are actively being developed and tested in clinical trials. Targeting an oncogenic driver may only prove effective if the mutation is present in most tumoral cells. Therefore, highly heterogeneous tumors may be refractory to these therapies. This makes tumor heterogeneity a major challenge in cancer therapy. Although heterogeneity has traditionally been attributed to genetic diversity within cancer cell populations, it is now widely recognized that human cancers are heterogeneous in almost all distinguishable phenotypic characteristics. Understanding the genetic variability and also the non-genetic influences of tumor heterogeneity will provide novel insights into how to reverse therapeutic resistance and improve cancer therapy.