Will Genetic Testing be the Answer to the Definition of Treatments in the Era of Precision Therapies?

With the increasing and fast development of molecular medicine, we can aspire to carry out treatments directed to the sickness of each patient, and with this practice the idealized precision medicine. Its objectives are not only survival and response rates, but also best quality of life with lowest toxicity, with more cost-effective choices for each single patient.Defining the complete genomic picture of all cancerous lesions, in the near future, is a major goal in Oncology that will benefit everyone. The further and recent use of liquid biopsies, processed by next generation sequencing , as a method to determine specific genetic mutations, has obtained clinical utility and validity in the metastatic scenario, with a predictive value. Further clinical trials need to be performed in surgical cases, so that specific gene mutations can be used as biomarkers, to evaluate residual disease, stratify risk of relapse (prognostic value) and identify the patients that will need adjuvant treatment besides the classical staging system. keywords: precision medicine, circulating tumor DNA, liquid biopsies, biomarkers Introduction In solid tumors, tissue biopsy has for long been the “gold standard” for histological diagnosis and immunohistochemical, genetic and molecular studies of the various neoplasms [1]. Traditionally, the anato-mical, pathological and the imaging tools allowed, in combination, an evaluation of each solid tumor and its staging according to the clinical classi-fication of Tumor, Nodule and Metastasis (TNM). To date most treatments in oncology are based on this staging and classification. Adding information obtained through molecular medicine is essential to optimize the therapy for each patient and each tumor. In 1948, circulating tumor deoxyribonucleic acid (ctDNA) was first identified in human blood by Mandel and Metals [2]. The ctDNA is actually the DNA released by the primary or metastatic neoplastic cells, being released into the bloodstream and which can being isolated from a peripheral blood with a simple blood test. The discovery of tumor DNA in blood samples in what has been defined as "liquid biopsy" may be the key to avoiding or at least diminishing the need for some invasive procedures. This new technique may be the key, or at least a temporary solution to obtain a broader view of tumor heterogeneity and with this spectrum of the disease, allow the identification of different mechanisms of resistance to different drugs, in clinical practice to tailor each treatment to a patient / specific neoplasia. An even more ambitious goal for liquid biopsies in the near future is the early detection of some neoplasms and thereby contribute to the overall reduction of cancer mortality. Technological Evolution One of the first challenges considered was how to discriminate the cDNA from DNA free from normal cells. It is now difficult to remember that, not yet for a long time, the biomarkers analysis was limited to 1-5 genes in the clinical routine. The sensitivity of the polymerase chain reaction (PCR) based on digital techniques has improved over time, however, with the increase in the number of biomarkers and the need for them to be analyzed simultaneously, several technical problems arise, as for example, the amount of sample required for DNA extraction. The new next-generation sequencing technology (NGS), allows, in just 10ng of DNA, to determine the detection of mutations, translocations or variations of copies in a large number of genes simultaneously. This NGS technique allows to save material and obtain a fast response with acceptable sensitivities and specificities [3], assuming an essential role for the major objective that is the understanding of the complexity of the cancer through the analysis of the genome by sequencing of the exom or of the entire tumor genome. At the American Society of Clinical Oncology (ASCO) in 2016, a study funded by Guardian Health Inc.