Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers. It is the
fourth leading cause of cancer-related death in the United States [
![Figure thumbnail gr1]()
[1]
]. Nearly 40,000 Americans are affected by this disease every year and more than half
of these individuals succumb to cancer-related complications [
[1]
]. Even with cases that are identified early and undergo surgical resection, the diagnosis
of PDA is associated with an overall 5-year survival rate of only 6% to 25% [
[2]
]. Although many resources and large genome-profiling studies have been completed (Fig. 1) [
3
,
4
], the clinical management of this disease has still made only modest strides in the
past 2 decades.
Fig. 1Progression model of pancreatic cancer, with arrows indicating where, for early detection,
prognostic markers (below the model in red) and predictive markers (below in blue) are needed. Precursor lesions are PanIN lesions (early, left side, to late, right
side) and invasive PDA is shown to the right of the figure.
(Modified from artist Jennifer Brumbaugh; with permission.)
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Advances in SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- American Cancer Society: cancer facts and figures.(Available at:) (2009)
- Surgical treatment of pancreatic cancer: the role of adjuvant and multimodal therapies.Eur J Surg Oncol. 2007; 33: 817-823
- Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.Science. 2009; 324: 217
- Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.Science. 2008; 321: 1801-1806
- Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.J Clin Oncol. 1997; 15: 2403-2413
- Pancreatologists: an endangered species?.Gastroenterology. 2010; 138: 1236
- Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial.J Clin Oncol. 2010; 28
- Albumin-bound paclitaxel: a next-generation taxane.Expert Opin Pharmacother. 2006; 7: 1041-1053
- Progression model for pancreatic cancer.Clin Cancer Res. 2000; 6: 2969-2972
- Prognostic versus predictive value of biomarkers in oncology.Eur J Cancer. 2008; 44: 946-953
- CA 19-9 to differentiate benign and malignant masses in chronic pancreatitis: is there any benefit?.Indian J Gastroenterol. 2009; 28: 24-27
- CA 19-9 as a marker for gastrointestinal cancers: a review.Ann Clin Biochem. 1998; 35: 364-370
- Specific antigen in serum of patients with colon carcinoma.Science. 1981; 212: 53-55
- Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704.J Clin Oncol. 2008; 26: 5918-5922
- Clinicopathological aspects of small pancreatic cancer.Pancreas. 2004; 28: 235-240
- Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer.Cancer Res. 1987; 47: 5501-5503
- Role of tumour markers, cytogenetics.Ann Oncol. 1999; 10: 145-149
- High sensitivity and specificity of CA 19-9 for pancreatic carcinoma in comparison to chronic pancreatitis. Serological and immunohistochemical findings.Pancreas. 1987; 2: 398-403
- Serum CA19-9 decline compared to radiographic response as a surrogate for clinical outcomes in patients with metastatic pancreatic cancer receiving chemotherapy.Pancreas. 2008; 37: 269-274
- Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques.J Exp Med. 1965; 121: 439-462
- Carcinoembryonic antigen as a target for therapeutic anticancer vaccines: a review.J Clin Oncol. 2002; 20: 2197-2207
- Prognostic relevance of CA 19-9, CEA, CRP, and LDH kinetics in patients treated with palliative second-line therapy for advanced pancreatic cancer.Tumour Biol. 2010; 31: 351-357
- CA 125: the past and the future.Int J Biol Markers. 1998; 13: 179-187
- Reactivity of a monoclonal antibody with human ovarian carcinoma.J Clin Invest. 1981; 68: 1331-1337
- CEA, CA 19-9, and CA 125 in the differential diagnosis of benign and malignant pancreatic diseases with or without jaundice.J Surg Oncol. 2007; 95: 142-147
- Molecular markers of pancreatic cancer: development and clinical relevance.Langenbecks Arch Surg. 2008; 393: 883-890
- Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16.J Biol Chem. 2001; 276: 27371-27375
- Serum Biomarker Panels for the Detection of Pancreatic Cancer.Clin Cancer Res. 2011; 17: 805-816
- Association between expression levels of CA 19-9 and N-acetylglucosamine-beta;1,3-galactosyltransferase 5 gene in human pancreatic cancer tissue.Pathobiology. 2004; 71: 26-34
- Markers of pancreatic cancer: working toward early detection.Clin Cancer Res. 2011; 17: 635-637
- Increased prevalence of precursor lesions in familial pancreatic cancer patients.Clin Cancer Res. 2009; 15: 7737-7743
- A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair.J Clin Oncol. 2008; 26: 3785-3790
- Identifying pancreatic cancer patients for targeted treatment: the challenges and limitations of the current selection process and vision for the future.Expert Opin Drug Deliv. 2010; 7: 273-284
- In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor.Clin Cancer Res. 2005; 11: 7508-7515
- Functional defects in the Fanconi anemia pathway in pancreatic cancer cells.Am J Pathol. 2004; 165: 651-657
- Screening and surveillance approaches in familial pancreatic cancer.Gastrointest Endosc Clin N Am. 2008; 18 (x): 535-553
- Can we screen high-risk individuals to detect early pancreatic carcinoma?.J Surg Oncol. 2000; 74: 243-248
- Update on familial pancreatic cancer.Adv Surg. 2010; 44: 293-311
- Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer.Cancer Cell. 2010; 18: 499-509
- DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer.J Clin Oncol. 2009; 27: 1806-1813
- SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer.Clin Cancer Res. 2009; 15: 4674-4679
- Pancreatic oncofetal antigen and carbohydrate antigen 19-9 in sera of patients with cancer of the pancreas.Clin Chem. 1989; 35: 405-408
- Chir Ital. 2000; 52 ([in Italian]): 369-377
- Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.Gastroenterology. 2001; 121: 640-645
- Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype.Br J Cancer. 1991; 64: 899-902
- Prospective study of CAM 17.1/WGA mucin assay for serological diagnosis of pancreatic cancer.Lancet. 1997; 349: 389-392
- Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma.J Cancer Res Clin Oncol. 1994; 120: 494-497
- Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma.Mod Pathol. 2005; 18: 779-787
- Comparison of tumor M2-pyruvate kinase (tumor M2-PK), carcinoembryonic antigen (CEA), carbohydrate antigens CA 19-9 and CA 72-4 in the diagnosis of gastrointestinal cancer.Anticancer Res. 2003; 23: 5089-5093
- Serum diagnosis of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass spectrometry.Clin Cancer Res. 2004; 10: 860-868
- Overexpression of synuclein-gamma in pancreatic adenocarcinoma.Cancer. 2004; 101: 58-65
- Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9.Clin Cancer Res. 2006; 12: 442-446
- Comprehensive proteomic analysis of human pancreatic juice.J Proteome Res. 2004; 3: 1042-1055
- Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach.Mol Cell Proteomics. 2006; 5: 157-171
- A mouse to human search for plasma proteome changes associated with pancreatic tumor development.PLoS Med. 2008; 5: e123
- Circulating tumor cells and emerging blood biomarkers in breast cancer.Curr Opin Oncol. 2010; 22: 552-558
- Circulating tumour cells in cancer patients: challenges and perspectives.Trends Mol Med. 2010; 16: 398-406
- Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.PLoS One. 2011; 6: e17014
- Diverse molecular functions of Hu proteins.Cell Mol Life Sci. 2008; 65: 3168-3181
Brody JR, Gonye GE. HuR’s role in gemcitabine efficacy: an exception or opportunity? WIREs RNA, in press.
- Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression.Cancer Res. 2004; 64: 189-195
- Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma.Cancer Res. 2005; 65: 2157-2161
- Prognostic role of HuR in hereditary breast cancer.Clin Cancer Res. 2007; 13: 6959-6963
- Tissue microarray analysis of 560 patients with colorectal adenocarcinoma: high expression of HuR predicts poor survival.Ann Surg Oncol. 2009; 16: 200-207
- HuR in the mammalian genotoxic response: post-transcriptional multitasking.Cell Cycle. 2003; 2: 412-414
- The ’RNA-binding ome’: future implications for chemotherapeutic efficacy.Future Oncol. 2009; 5: 1317-1319
- Role of the RNA-binding protein HuR in colon carcinogenesis.Oncogene. 2003; 22: 7146-7154
- Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR.J Biol Chem. 1998; 273: 6417-6423
- Identification of a target RNA motif for RNA-binding protein HuR.Proc Natl Acad Sci U S A. 2004; 101: 2987-2992
- HuR recruits let-7/RISC to repress c-Myc expression.Genes Dev. 2009; 23: 1743-1748
- ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5’UTR.Genes Dev. 2002; 16: 3087-3099
- Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells.Nucleic Acids Res. 2006; 34: 3988-3999
- The ELAV RNA-stability factor HuR binds the 5’-untranslated region of the human IGF-IR transcript and differentially represses cap-dependent and IRES-mediated translation.Nucleic Acids Res. 2005; 33: 2962-2979
- ARED 3.0: the large and diverse AU-rich transcriptome.Nucleic Acids Res. 2006; 34: D111-D114
- Global dissociation of HuR-mRNA complexes promotes cell survival after ionizing radiation.EMBO J. 2011; 30: 1040-1053
- RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer.J Clin Oncol. 2006; 24: 4731-4737
- Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2.Mod Pathol. 2006; 19: 1261-1269
- HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients.Ann Surg. 2010; 252 ([discussion: 505–6]): 499-505
- Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.Gastroenterology. 2009; 136: 187-195
- In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant.Cancer Res. 2005; 65: 9510-9516
- Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines.Pharmacogenet Genomics. 2006; 16: 429-438
- Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma.Oncogene. 2009; 28: 2903-2909
- In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-based chemotherapy.Cancer Invest. 2009; 28: 172-180
- Pharmacogenetics in pancreatic cancer. Highlights from the 45th ASCO annual meeting. Orlando, FL, USA. May 29-June 2, 2009.JOP. 2009; 10: 357-360
- Single nucleotide polymorphism in RECQL and survival in resectable pancreatic adenocarcinoma.HPB (Oxford). 2009; 11: 435-444
- The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase.Cancer Res. 2009; 69: 4567-4572
- Reduction of pp32 expression in poorly differentiated pancreatic ductal adenocarcinomas and intraductal papillary mucinous neoplasms with moderate dysplasia.Mod Pathol. 2007; 20: 1238-1244
- Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.J Clin Oncol. 2007; 25: 1960-1966
- Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells.J Biol Chem. 2004; 279: 3941-3948
- Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy.Proc Natl Acad Sci U S A. 2010; 107: 10791-10798
- Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors.Cancer Res. 2008; 68: 8322-8332
- DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.Science. 2011; 331: 1199-1203
- Short RNAs: how big is this iceberg?.Curr Biol. 2010; 20: R110-R113
- A compendium of potential biomarkers of pancreatic cancer.PLoS Med. 2009; 6: e1000046
Article info
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
