Genomics in Cancer of Unknown Primary: Utility in Modern Clinical Practice

Abstract

Cancer of unknown primary (CUP) is defined as metastatic cancer where the primary tumour responsible for metastatic spread cannot be identified despite thorough diagnostics. It has a very poor prognosis, is rapidly progressive, and has limited treatment options beyond empirical chemotherapy. Modern genomic advances play a role in identifying the primary tissue of origin (TOO) and in allowing molecular targeted therapies and immunotherapies to be used in the treatment of CUP patients. Whole genome and whole transcriptome sequencing produce vast amounts of data, and predictive algorithms and artificial intelligence can be used to make this data clinically actionable. Recent trials have shown that using genomic data in clinical decision-making improves outcomes for CUP patients. Liquid biopsies are an exciting development that allow for repeated genomic analysis throughout treatment or when tissue is difficult to obtain. Genomics should be used routinely in the care of CUP patients, at diagnosis and to aid treatment decisions.

Keywords: Cancer genomics; Cancer of unknown primary; Liquid biopsy; Molecular tumour board; Molecularly guided therapy; Tissue of origin; Whole genome sequencing.