What biomarkers (if any) for precise medicine?

advent of the OMIC technologies has strongly evolved the knowledge about the origin, the type and the response to therapy of a given tumor. To date we are aware that the epigenetic and genomic landscapes of tumors which origin, histopathological diagnoses and clinical stages are almost identical can be highly heterogeneous. Initially, the Human Genome Project represented the reference map for the human genome and provided the ideal background for the development of technology and analytic tools to decipher and rationalize enormous quantities of genomic data [1]. Subsequently, the National Research Council reported on the requirement of a precise taxonomy of human disease based on the continuous flow of molecular data originating from the OMIC approaches. This led The Cancer Genome Atlas (TGCA) and the International Cancer Genome Consortium (ICGC) toward the molecular taxonomy of different human cancers. A large spectrum of gene mutations has been identified [1]. They can be categorized in: (a) passenger mutations that are the majority and may be biologically inactive and clinically irrelevant; (b) driver mutations whose activity is required for the aberrant growth, survival and chemoresistance of human cancers. Driver mutations have been the main molecular targets to be tackled with " smart " drugs, thus providing the rationale for precise medicine. Next Generation Sequence (NGS) technology has enabled to identify actionable targets such as EGFR in lung cancer and BRAF in melanoma [1,2]. Since these drugs benefit only those patients carrying specific driver mutations the identification of biomarkers that can predict treatment responses is vital for the success of the precise cancer therapy and for the development of anticancer drugs. EGFR mutations are considered biomarkers for selecting lung cancer patients for the treatment with EGFR inhibitors [3]. Gefinitib and erlotinib represent the first choice for the treatment of lung cancer patients carrying EGFR mutations and prolong significantly the progression-free survival of the selected patients. Despite it, both gefinitib and erlotinib cannot be used to treat all lung cancer patients harbouring EGFR mutations due to mutation site heterogeneity which negatively impacts on the affinity of EGFR inhibitors to the mutated EGFR and consequently of the efficacy of the treatment. Lung cancer patients develop resistance to EGFR inhibitors Editorial due mostly common (50% of EGFR mutated lung cancer patients) to additional EGFRT90M mutation [3]. Unlike EGFR, other driver mutations as those affecting the p53 gene, the most frequent target of genetic alterations in human cancers, …