title: From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers.
abstract: Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food &amp; Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.
authors.affiliation: Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece. ikyrochristos@hotmail.com.|Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece. ikyrochristos@hotmail.com.
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Kyrochristos
authors.affiliation: Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece. gglantzounis@gmail.com.
authors.forename: Georgios K
authors.initials: GK
authors.lastname: Glantzounis
authors.affiliation: Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece. deziogas@hotmail.com.|Department of Surgery, 'G. Hatzikosta' General Hospital, 45001 Ioannina, Greece. deziogas@hotmail.com.
authors.forename: Demosthenes E
authors.initials: DE
authors.lastname: Ziogas
authors.affiliation: General Hospital of Grevena, 51100 Grevena, Greece. gizas24@yahoo.gr.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gizas
authors.affiliation: 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece. schizasad@gmail.com.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Schizas
authors.affiliation: Department of Plastic Surgery, Ioannina University School of Medicine, 45110 Ioannina, Greece. elykoudi@cc.uoi.gr.
authors.forename: Efstathios G
authors.initials: EG
authors.lastname: Lykoudis
authors.affiliation: 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece. evangelosf@hotmail.com.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Felekouras
authors.affiliation: Third Department of Surgery, Attikon General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece. anmach@med.uoa.gr.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Machairas
authors.affiliation: Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece. chkatsios@gmail.com.
authors.forename: Christos
authors.initials: C
authors.lastname: Katsios
authors.affiliation: 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece. theodlia@otenet.gr.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Liakakos
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, China. chocs@ha.org.hk.
authors.forename: William C
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece. droukos@uoi.gr.|Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece. droukos@uoi.gr.|Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece. droukos@uoi.gr.
authors.forename: Dimitrios H
authors.initials: DH
authors.lastname: Roukos
mesh_terms: D001660:Biliary Tract Diseases / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics*; D005791:Patient Care; D012015:Reference Standards; D057170:Translational Research, Biomedical
keywords: clinical implications; hepatobiliary and pancreatic (HBP) cancers; next-generation sequencing (NGS)