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.

Life and death of circulating cell-free DNA

“…134,135 The observation that cfDNA could integrate into the genomes of healthy cells led to the development of the genometastasis hypothesis. [134][135][136][137][138] However, further studies showed that the uptake of vesicles that contain DNA depends on the condition of the cell recipient. For example, transformed cell line variants are more sensitive to exosome-mediated uptake than other cell lines.…”

Increased level and fragmentation of plasma circulating cell-free DNA are diagnostic and prognostic markers for renal cell carcinoma

“…Blood-based tests, also known as liquid biopsy, can offer a potential alternative measure that overcomes the problems posed by traditional methods. Liquid biopsy such as circulating tumor cells or circulating cell-free DNA (cfDNA) constitutes a promising and less invasive technique [ 4 ]. However, no satisfactory blood-based markers for RCC currently exist, creating an urgent need for the identification of new molecular markers.…”

Cancer Stem Cells: «Emergency Service» for Tumors Under Generalized Cellular Stress

“…Другим возможным механизмом формирования плюрипотентного фенотипа у опухолевых клеток может быть феномен «генометастазирования» [176]. Предполагается, что экстраклеточная двуцепочечная ДНК, выделившаяся из клеток, погибших в результате апоптоза или некроза, как первичного, так и вторичного, может поглощаться раковыми клетками, прошедшими первые стадии дифференцировки/коммитирования, но еще сохранившими такую базовую характеристику СРК, как способность захватывать фрагменты экстраклеточной двуцепочечной ДНК.…”