Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis theory

Abstract

Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism, not yet fully understood. What is almost beyond doubt is that circulatory system is crucial for cancer propagation. Regarding this system, much attention has been recently paid to liquid biopsy. This technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic, prognostic and follow-up of patients. Whereas CTCs tend to be scarce in serum and plasma from cancer patient, abundant circulating nucleic acids can be detected in the same location. This fact, together with the genetic origin of cancer, stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis, a recently discovered phenomenon called Genometastasis. This innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory system. What is more, many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of oncogenes. In this review, we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this theory. Our objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

Keywords: Genometastasis; Cancer metastasis; Circulating Nucleic acids: Circulating tumor cells; Liquid biopsy; Exosomes; Virtosomes

Core tip: Liquid biopsy not only constitutes a promising tool for cancer diagnostic and patient follow-up but also it may help in the comprehension of metastasis. This technique has revealed how circulating tumor cells are limited in blood, while circulating nucleic acids are much more abundant. This property, together with the demonstrated capability of circulating nucleic acids to transform susceptible cells, strongly support the theory of genometastasis. This theory sustains that cancer propagation relies on gene transfer from malignant cells to normal cells. We pretend to gather all these concepts, also including cell-to-cell communication mechanisms to demonstrate this phenomenon.