Περίληψη:
Introduction: The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy. Expert commentary: Despite the many overenthusiastic original and opinion reports, we have critically reviewed available NGS studies, with focus on the challenges to achieve clinical implications. Based on the recommendations for valid identification of clinically crucial genomic alterations (GAs) by NGS, we propose NGS integration into appropriately designed clinical trials. Furthermore, valid detection of genomic heterogeneity enables the conduction of clinical trials investigating the efficacy both of GAs as prognostic and predictive tools, as well as the discovery of novel oncotargets, on the basis of an early drug development strategy. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
Συγγραφείς:
Ziogas, D.E.
Kyrochristos, I.D.
Glantzounis, G.K.
Christodoulou, D.
Felekouras, E.
Roukos, D.H.
Λέξεις-κλειδιά:
regorafenib; sorafenib, Article; bile duct carcinoma; cancer prognosis; cancer surgery; carcinogenesis; gene mutation; gene targeting; genetic heterogeneity; human; liver cancer; liver cell carcinoma; next generation sequencing; overall survival; phase 3 clinical trial (topic); randomized controlled trial (topic); RNA sequence; survival rate; translational research; whole exome sequencing; whole genome sequencing; genetics; liver tumor; prognosis, Carcinoma, Hepatocellular; Cholangiocarcinoma; Humans; Liver Neoplasms; Prognosis; Whole Genome Sequencing
