Liquid Biopsy perspectives theranostics and personalized oncology

The current limitations of cancer diagnosis and molecular profi ling based on invasive tissue biopsies or clinical imaging have led to the development of the Liquid Biopsy fi eld (LB), includes the isolation of Circulating Tumor Cells (CTCs), circulating free or tumor DNA (cfDNA or ctDNA), Extracellular Vesicles (EVs), and TumorEducated Platelets (TEPs) from body fl uid samples and their molecular characterization to identify biomarkers for early cancer diagnosis, prognosis, therapeutic prediction, and follow-up. As cancers grow, evolve, and spread, they shed circulating tumor cells (CTCs), as well as other tumor-associated cells and products, into the bloodstream. Capturing and analyzing CTCs or other tumor-associated cells and products from a patient’s blood sample can provide insight into particular cancer’s biology, response to treatment, and/ or potential therapeutic targets. CTCs are heterogeneous; a pressing question concerns which CTCs represent those directly involved in metastasis, the major cause of cancer-related death. The aim of this review, is to describe the biological principles underlying the Liquid Biopsy (LB) concept and to discuss how functional studies can expand the clinical applications of these circulating biomarkers. Perspective Study Liquid Biopsy perspectives theranostics and personalized oncology C Daniel Ascencio González* Hospital Ángeles del Pedregal, Camino a Santa Teresa 1055-615Col Héroes de Padierna, Mayor’s Offi ce Magdalena Contreras C.P.10800 Mexico City, Mexico Received: 15 August, 2020 Accepted: 12 September, 2020 Published: 14 September, 2020 *Corresponding author: C Daniel Ascencio González, Hospital Ángeles del Pedregal, Camino a Santa Teresa 1055-615Col Héroes de Padierna, Mayor’s Offi ce Magdalena Contreras C.P.10800 Mexico City, Mexico, Tel: 55556858 76; E-mail:


Introduction
GLOBOCAN 2018 estimates that the incidence and mortality from cancer worldwide were 18.1 million and 9.6 million deaths, respectively is responsible for one in eight deaths worldwide. It encompasses more than 100 distinct diseases with diverse risk factors and epidemiology which originate from most of the cell types and organs of the human body and which are characterized by unrestrained proliferation of cells that can invade beyond normal tissue boundaries and metastasize to distant organs [1]. There is great potential for genome sequencing to enhance patient care through improved diagnostic sensitivity and more precise therapeutic targeting.
To maximize this potential, genomics strategies that have been developed for genetic discovery -including DNA-sequencing technologies and analysis algorithms -need to be adapted to fi t clinical needs. The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of tumors, constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis [2].
All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells, cancer development is based on two constituent processes, the continuous acquisition of heritable genetic variation in individual cells by more-or-less random mutation and natural selection acting on the resultant phenotypic diversity. Now, it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes. These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed [3].
The identifi cation of the variations of the tumor genotype demonstrate the heterogeneity parameter that predicts the therapeutic response, subpopulations of Cancer Cells (CC), unique genomes can exist within the same tumor and evolve over time (intratumor heterogeneity), which is used for characterization, monitoring of clonal dynamics and identifi cation of therapeutic resistances [4]. potential for non-invasive molecular diagnostics and may represent a novel therapeutic delivery system [5].

Tumor diagnosis
Tissue biopsies are laborious, and stressful for the patient, generally unlikely to be repeated during disease progression.
For these reasons, the majority of clinical decisions in the metastatic context tend to be based on biopsies of the primary cancer, and frequently do not represent the genetic profi le that allows establishing the treatment of the disease, particularly of metastases [6]. The current diagnosis of tumors is studied with a tissue biopsy, it is considered the gold standard, however, it has many limitations to have an accurate diagnosis, it determines its origin and genetic profi le, although it only allows studying a static and limited sample and eventually It is diffi cult to obtain, it has low sensitivity and precision, it does not allow determining heterogeneity or invasiveness, it is incompatible with longitudinal clinical follow-up, and it does not detect an early-stage tumor or residual tumors [7].
Specifi cally it does not offer an accurate diagnosis.
In oncology, detection of cfDNA derived from tumors, also known as ctDNA, has been challenging for three primary  [20,21].
Composite biomarker panels need to be tested in clinical studies with well-established endpoints to demonstrate clinical validity and utility, which will be key to introduce LB into clinical practice. Furthermore, experimental studies must gain more knowledge on the biology of LB markers, which can then in turn be retranslated to the bedside to improve the clinical use of LB analytes. The biggest challenge is the low concentration of ctDNA in the blood. Although some NGS-based protocols improve the sensitivity of ctDNA assays in many different ways, the tradeoff between sensitivity and cost is still the greatest concern in practice. In the future, other sources of information apart from ctDNA should be combined to increase sensitivity and specifi city. Moreover, applying ctDNA sequencing to cancer screening provides us with a good opportunity to collect longitudinal data to create a better disease classifi cation model. Provide a cost-effective, fast, reproducible and non-invasive source for early cancer diagnosis and prognostic monitoring. In addition, analysis of circulating tumor-derived factors or the tumor circulome in the liquid biopsies can capture the clonal heterogeneity of these tumors unlike tissue biopsies. Various LB samples can be combined to improve the chances of cancer diagnosis, and sequential real-time biopsies will further aid in the early identifi cation of therapy-resistant tumors.
Furthermore, detection and characterization of minimal residual disease after initial therapy can also be improved by analyzing LB.