Liquid Biopsies for Monitoring Temporal Genomic Heterogeneity in Breast and Colon Cancers

Abstract

Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer. The implementation and standardization of both approaches are still needed to achieve the required sensitivity and specificity to successfully analyze heterogenous tumours, but pivotal studies, in particular those concerning colorectal cancer, have shown the feasibility and usefulness of liquid biopsy for monitoring the Darwinian clonal evolution from an early to a metastatic stage.

Keywords: Breast cancer; Cell-free DNA; Circulating tumour DNA; Circulating tumour cells; Colorectal cancer; Genomic heterogeneity; Liquid biopsy.