Evaluation and consequences of heterogeneity in the circulating tumor cell compartment

A growing understanding of the molecular biology of cancer and the identification of specific aberrations driving cancer evolution have led to the development of various targeted agents. Therapeutic decisions concerning these drugs are often guided by single biopsies of the primary tumor. Yet, it is well known that tumors can exhibit significant heterogeneity and change over time as a result of selective pressure. Circulating tumor cells (CTCs) are shed from various tumor sites and are thought to represent the molecular landscape of a patient's overall tumor burden. Moreover, a minimal-invasive liquid biopsy facilitates monitoring of clonal evolution during therapy pressure and disease progression in real-time. While more information becomes available regarding heterogeneity among CTCs, comparison between these studies is needed. In this review, we focus on the genomic and transcriptional heterogeneity found in the CTC compartment, and its significance for clinical decision making.