Τίτλος:
From clinical standards to translating next-generation sequencing research into patient care improvement for hepatobiliary and pancreatic cancers
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 & 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. © 2017 by the authors; licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Kyrochristos, I.D.
Glantzounis, G.K.
Ziogas, D.E.
Gizas, I.
Schizas, D.
Lykoudis, E.G.
Felekouras, E.
Machairas, A.
Katsios, C.
Liakakos, T.
Cho, W.C.
Roukos, D.H.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
axitinib; bevacizumab; brivanib; cediranib; cetuximab; elpamotide; erlotinib; fluoropyrimidine; gemcitabine; linifanib; pegargiminase; ramucirumab; rigosertib; sorafenib; sunitinib; tamoxifen; tipifarnib, bile duct cancer; cancer adjuvant therapy; cancer survival; cell heterogeneity; chemoradiotherapy; drug efficacy; gene mutation; hepatobiliary system cancer; human; liver cell carcinoma; meta analysis (topic); next generation sequencing; nonhuman; pancreas adenocarcinoma; pancreas cancer; patient care; personalized medicine; phase 2 clinical trial (topic); phase 3 clinical trial (topic); randomized controlled trial (topic); Review; therapy resistance; whole exome sequencing; whole genome sequencing; biliary tract disease; genetics; high throughput sequencing; pancreas tumor; procedures; standard; translational research, Biliary Tract Diseases; High-Throughput Nucleotide Sequencing; Humans; Pancreatic Neoplasms; Patient Care; Reference Standards; Translational Medical Research
DOI:
10.3390/ijms18010180
