Mining nucleic acid “omics” to boost liquid biopsy in cancer

Treatments for cancer patients are becoming increasingly complex, and there is a growing desire from clinicians and patients for biomarkers that can account for this complexity to support informed decisions about clinical care. To achieve precision medicine, the new generation of biomarkers must reflect the spatial and temporal heterogeneity of cancer biology both between patients and within an individual patient. Mining the different layers of 'omics in a multi-modal way from a minimally invasive, easily repeatable, liquid biopsy has increasing potential in a range of clinical applications, and for improving our understanding of treatment response and resistance. Here, we detail the recent developments and methods allowing exploration of genomic, epigenomic, transcriptomic, and fragmentomic layers of 'omics from liquid biopsy, and their integration in a range of applications. We also consider the specific challenges that are posed by the clinical implementation of multi-omic liquid biopsies.