T33

Abstract

Blood-derived biomarkers, such as circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), are a valuable source of molecular genetic data for tumours they spring from. In translational cancer research, the “liquid biopsy” concept has been put forward to denote the detection and molecular characterization of these biomarkers.

The idea of liquid biopsy is based on a hypothesis that profiles of somatic mutations in CTCs and ctDNA are identical to those in the original tumour. Therefore, the mutation status of the source tumour can be revealed through the molecular analysis of the CTCs and ctDNA obtained from the blood. The major advantages of liquid biopsy are an essentially decreased invasiveness (no need for tissue biopsy, surgery or bronchoscopy) and an ability to carry out the analysis at patient’s follow up (e.g. to monitor for residual disease).

However, both the CTCs and ctDNA are not abundant in the bloodstream and their capture is technically challenging. Also, due to tumour heterogeneity, the CTCs may not fully represent the entire tumour, while ctDNA is naturally fragmented and degraded, so its utility for genetic analysis may be limited. Finally, the DNA extracted from CTCs and, especially, ctDNA are “contaminated” by DNA from non-tumour cells from the bloodstream raising a challenge of detecting mutant DNA among significantly prevailing wild-type DNA.

Some of these issues can be overcome by using such advanced techniques as BEAMing, digital PCR or ultra-deep sequencing, but their use in standard clinical settings is limited by the need for special equipment and associated costs. Inexpensive and less sophisticated, but still highly sensitive and specific, approaches, such as COLD-PCR or wild-type blocking PCR, are also available to detect “druggable” mutations in CTCs and ctDNA.

Application of these approaches of liquid biopsy in clinical practice may be highly beneficial for personalized care of lung cancer patients.