Pancreatic cancer genomics: where can the science take us?

  title={Pancreatic cancer genomics: where can the science take us?},
  author={Janet S Graham and Nigel B. Jamieson and Robert Rulach and Sean M. Grimmond and David K. Chang and Andrew V. Biankin},
  journal={Clinical Genetics},
The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing and the annual death‐to‐incidence ratio approaches one. This is a figure that has not changed for several decades. Surgery remains the only chance of cure; however, only less than 20% of patients are amenable to operative resection. Despite successful surgical resection, the majority of the patients still succumb to recurrent metastatic disease. Therefore, there is an urgent need to develop novel therapeutic… 
Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic Cancer
An update is provided on the role of EUS FNA as a diagnostic tool, as well as a source of genetic material which can be used both for molecular analysis and for the creation of valuable preclinical disease models.
Kirsten Rat Sarcoma Viral Oncogene Homologue(KRAS) mutations in the occurrence and treatment of pancreatic cancer.
To better design chemical drugs, this review based on the biological functions of KRAS summarized the types ofKRAS mutations and their relationship with pancreatic cancer and included the downstream signaling pathway Raf-MEK-ERK, PI3K-AKT, RalGDS-Ral of KRas and the current medicinal treatment methods for KRAS mutations are reviewed.
Pancreatic Cancer: Historical Problem as well as Personal and Current Solutions which have Prospects in Translational Medicine
It is concluded that its replication would lead to obtaining the breakthrough as regards developing that target therapy which could conduce to cancer cure, this being inclusive of the pancreas.
Loss of BAP1 Expression Is Very Rare in Pancreatic Ductal Adenocarcinoma
It is concluded that, in contrast to intrahepatic cholangiocarcinoma, loss of expression of BAP1 occurs very rarely in pancreatic ductal adenocarc inoma, and therefore B AP1 inactivation is unlikely to be a frequent driver abnormality in Pancreatic adenOCarcinomas.
Novel Molecular Targets and Mechanisms Involved in the Invasion and Metastasis of Pancreatic Cancer
Recent advances in novel molecular targets that regulate the invasion and metastasis of PDAC cells are summarized and how they are targeted for developing diagnostic and therapeutic tools for combating PDAC is summarized.
Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens
dPCR performs sensitive and accurate mutation analysis in pancreas FNAs, detecting not only the dominant mutation subtype, but also the additional rare mutation subtypes representing tumor heterogeneity.
[Research Progress of Mechanisms on Intracranial Metastasis of Non-small Cell Lung Cancer after Clinical Benefit from EGFR-TKI].
The mechanisms on intracranial metastasis of NSCLC after clinical benefit from EGFR-TKI are discussed.
Double germline mutations in APC and BRCA2 in an individual with a pancreatic tumor
The impact of a double germline mutation in two tumor predisposition genes in one individual and proven heterogeneity of multiple cases of pancreatic tumors in one family is outlined and the importance of family studies is illustrated.
Selective cytotoxicity of vanadium complexes on human pancreatic ductal adenocarcinoma cell line by inducing necroptosis, apoptosis and mitotic catastrophe process.
This research showed selective cytotoxic effect of vanadium complexes, containing phenanthroline and quinoline as an organic ligands, against human pancreatic ductal adenocarcinoma cell line (PANC-1), compared to non-tumor human immortalized pancreas duct epithelial cells (hTERT-HPNE).
Iterative data multiplexing (IDM) supports elucidation of drug targets from functional genomics
The value of conducting high throughput functional genomic screening campaigns has been the subject of some debate over recent years, where a lack of reproducibility and preclusion of the


The molecular and cellular heterogeneity of pancreatic ductal adenocarcinoma
Current standard therapies for pancreatic ductal adenocarcinoma have failed to attenuate the aggressiveness of this disease or confer notable improvements in survival, and the lack of success of conventional empiric therapy can be partly attributed to the underlying heterogeneity of pancreatic tumors.
Changing the paradigm in conducting randomized clinical studies in advanced pancreatic cancer: an opportunity for better clinical development.
  • J. Tabernero, T. Macarulla
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2009
The more mature data of the study being published now show that the combination of gem citabine with capecitabine has an increased RR, a statistically significant increase in PFS, and a trend towards improvement in OS over single-agent gemcitABine treatment.
Stromal expression of SPARC in pancreatic adenocarcinoma
Key preclinical and clinical data describing the role of SPARC in PDAC biology, the properties, and mechanisms of delivery of drugs that interact with SPARC are focused on and the proof-of-concept clinical trials using nab-paclitaxel are discussed.
HENT1 tumor levels to predict survival of pancreatic ductal adenocarcinoma patients who received adjuvant gemcitabine and adjuvant 5FU on the ESPAC trials.
The samples collected from the adjuvant ESPAC1/3 randomized trials have provided a unique opportunity to assess to REMARK standards the therapeutic predictability of hENT1 in patients undergoing resection for pancreatic cancer.
Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer
Mutation status of the v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR gene copy number (GCN) were evaluated as predictive markers in 26% of patients who had tumor samples available for analysis.
The patterns and dynamics of genomic instability in metastatic pancreatic cancer
It is found that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint, and phylogenetic trees across metastases show organ-specific branches.
Hent1 expression in patients with pancreatic cancer treated with gemcitabine after curative intended resection: Results from the CONKO-001 trial.
ConKO-001, a prospective randomized phase III study investigated the role of adjuvant gemcitabine (gem) as compared to observation and found hent1 high was defined as unequivocal membranous staining in more than 50% of tumor cells, all other cases were classified as hENT1 low.
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.
Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.
Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.