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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 10, 2017; 8(5): 378-388
Published online Oct 10, 2017. doi: 10.5306/wjco.v8.i5.378
Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis theory
Ana García-Casas, Dolores C García-Olmo, Damián García-Olmo
Ana García-Casas, Universidad Complutense de Madrid, 28050 Madrid, Spain
Dolores C García-Olmo, Centre de Recerca Experimental Biomèdica Aplicada(CREBA), IRBLLEIDA, 25138 Lleida, Spain
Damián García-Olmo, Department of Surgery, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, 28050 Madrid, Spain
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Damián García-Olmo, MD, PhD, Director, Professor, Surgeon, Department of Surgery, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, Avda Reyes Católicos 2, 28050 Madrid, Spain. damian.garcia@uam.es
Telephone: +34-669-845297
Received: March 17, 2017
Peer-review started: March 22, 2017
First decision: July 10, 2017
Revised: August 3, 2017
Accepted: September 5, 2017
Article in press: September 5, 2017
Published online: October 10, 2017
Processing time: 191 Days and 9.8 Hours
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.