The complexity of pancreatic ductal cancers and multidimensional strategies for therapeutic targeting

Journal of Pathology

Volumn 223, Issue 2, 2011, Pages 296-307

  Kern, Scott E ^a   Shi, Chanjuan ^a   Hruban, Ralph H ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

carcinoma; gene; genetic; heterogeneity; pancreas; personalized treatment; therapy

Indexed keywords

CANCER STAGING; GENE EXPRESSION; GENE MUTATION; GENE TARGETING; GENETIC VARIABILITY; HUMAN; PANCREAS CANCER; PANCREAS DUCT; PRIORITY JOURNAL; REVIEW;

EID: 78650017792     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.2813     Document Type: Review

References (85)

1. Jones S, Zhang X, Parsons DW, et al., Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-1806.
2. Hulst SPL,. Zur Kenntnis der Genese des Adenokarzinoms und Karzinoms des Pankreas [trans. van Heek T, Koopman V]. Virchows Arch B 1905; 180: 288-316.
3. Hruban RH, Wilentz R, Kern SE,. Genetic progression in the pancreatic ducts. Am J Pathol 2000; 156: 1821-1825.
4. Caldas C, Hahn SA, Hruban RH, et al., Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Res 1994; 54: 3568-3573.
5. van Heek NT, Meeker AK, Kern SE, et al., Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol 2002; 161: 1541-1547.
6. +. Am J Pathol 1998; 152: 1501-1507.
7. Westra WH, Sturm P, Drillenburg P, et al., K-ras oncogene mutations in osteoclast-like giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium. Am J Surg Pathol 1998; 22: 1247-1254.
8. Iacobuzio-Donahue CA, Fu B, Yachida S, et al., DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009; 27: 1806-1813.
9. Montgomery E, Wilentz RE, Argani P, et al., Analysis of anaphase figures in routine histologic sections distinguishes chromosomally unstable from chromosomally stable malignancies. Cancer Biol Ther 2003; 2: 248-252.
10. Olive KP, Jacobetz MA, Davidson CJ, et al., Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324: 1457-1461.
11. Tascilar M, Offerhaus GJ, Altink R, et al., Immunohistochemical labeling for the Dpc4 gene product is a specific marker for adenocarcinoma in biopsy specimens of the pancreas and bile duct. Am J Clin Pathol 2001; 116: 831-837.
12. McCarthy DM, Maitra A, Argani P, et al., Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases. Appl Immunohistochem Mol Morphol 2003; 11: 238-243.
13. Sebastiani V, Ricci F, Rubio-Viqueira B, et al., Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res 2006; 12: 2492-2497.
14. Spratlin J, Sangha R, Glubrecht D, et al., The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res 2004; 10: 6956-6961.
15. Laffan TA, Horton KM, Klein AP, et al., Prevalence of unsuspected pancreatic cysts on MDCT. Am J Roentgenol 2008; 191: 802-807.
16. Lee KS, Sekhar A, Rofsky NM, et al., Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol; 105: 2079-2084.
17. Winter JM, Ting AH, Vilardell F, et al., Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res 2008; 14: 412-418.
18. Schutte M, Hruban RH, Geradts J, et al., Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997; 57: 3126-3130.
19. Parsi MA, Li A, Li CP, et al., DNA methylation alterations in endoscopic retrograde cholangiopancreatography brush samples of patients with suspected pancreaticobiliary disease. Clin Gastroenterol Hepatol 2008; 6: 1270-1278.
20. + T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 2004; 200: 297-306.
21. Kondo H, Hazama S, Kawaoka T, et al., Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. Anticancer Res 2008; 28: 379-387.
22. Huang AY, Golumbek P, Ahmadzadeh M, et al., Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994; 264: 961-965. (Pubitemid 24196166)
23. Le DT, Pardoll DM, Jaffee EM,. Cellular vaccine approaches. Cancer J; 16: 304-310.
24. Peggs KS, Quezada SA, Chambers CA, et al., Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 2009; 206: 1717-1725.
25. Hassan R, Ebel W, Routhier EL, et al., Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Cancer Immun 2007; 7: 20.
26. Day JD, Digiuseppe JA, Yeo C, et al., Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms. Hum Pathol 1996; 27: 119-124.
27. Yamanaka Y, Friess H, Kobrin MS, et al., Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 1993; 13 (3): 565-569.
28. Kwak EL, Jankowski J, Thayer SP, et al., Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006; 12: 4283-4287.
29. Philip PA, Benedetti J, Corless CL, et al., Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28 (22): 3605-3610.
30. Safran H, Iannitti D, Ramanathan R, et al., Herceptin and gemcitabine for metastatic pancreatic cancers that overexpress HER-2/neu. Cancer Invest 2004; 22: 706-712.
31. Almoguera C, Shibata D, Forrester K, et al., Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53: 549-554.
32. Wilentz RE, Goggins M, Redston M, et al., Genetic, immunohistochemical, and clinical features of medullary carcinomas of the pancreas: a newly described and characterized entity. Am J Pathol 2000; 156: 1641-1651.
33. Kastrinos F, Mukherjee B, Tayob N, et al., Risk of pancreatic cancer in families with Lynch syndrome. J Am Med Assoc 2009; 302: 1790-1795.
34. Hunter C, Smith R, Cahill DP, et al., A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 2006; 66: 3987-3991.
35. Hempen PM, Zhang L, Bansal RK, et al., Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers. Cancer Res 2003; 63: 994-999.
36. Rozenblum E, Schutte M, Goggins M, et al., Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res 1997; 57: 1731-1734.
37. Gruis NA, Sandkuiji LA, van der Velden PA, et al., CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families. Melanoma Res 1995; 9: 169-177.
38. Lynch HT, Fusaro RM,. Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome. Pancreas 1991; 6: 127-131.
39. Whelan AJ, Bartsch D, Goodfellow PJ,. Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N Engl J Med 1995; 333: 975-977.
40. Serrano M, Hannon GJ, Beach D,. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993; 366: 704-707.
41. Hahn SA, Hoque ATMS, Moskaluk CA, et al., Homozygous deletion map at 18q21.1 in pancreatic cancer. Cancer Res 1996; 56: 490-494.
42. Lievre A, Bachet JB, Le Corre D, et al., KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006; 66: 3992-3995.
43. Jiang Y, Mackley H, Cheng H, et al., Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway treatment. Biomark Med 2010; 4: 535-541.
44. Vassilev LT, Vu BT, Graves B, et al., In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303: 844-848.
45. Giardiello FM, Brensinger JD, Tersmette AC, et al., Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000; 119: 1447-1453.
46. Lowenfels AB, Maisonneuve P, DiMagno EP, et al., Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 1997; 89 (6): 442-446.
47. Goggins M, Schutte M, Lu J, et al., Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996; 56: 5360-5364.
48. Murphy KM, Brune KA, Griffin C, et al., Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res 2002; 62: 3789-3793.
49. Jones S, Hruban RH, Kamiyama M, et al., Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009; 324: 217.
50. van der Heijden MS, Kern SE,. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res 2003; 63: 2585-2588.
51. Couch FJ, Johnson MR, Rabe K, et al., Germ line Fanconi anemia complementation group C mutations and pancreatic cancer. Cancer Res 2005; 65: 383-386.
52. Su GH, Hruban RH, Bova GS, et al., Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 1999; 154: 1835-1840.
53. Su GH, Hruban RH, Bansal RK, et al., Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 1999; 154: 1835-1840.
54. Sahin F, Maitra A, Argani P, et al., Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Mod Pathol 2003; 16: 686-691.
55. Canto MI, Goggins M, Hruban RH, et al., Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 2006; 4: 766-781; quiz, 665.
56. Witt H, Luck W, Hennies HC, et al., Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000; 25: 213-216.
57. Bryant HE, Schultz N, Thomas HD, et al., Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913-917.
58. Farmer H, McCabe N, Lord CJ, et al., Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434: 917-921.
59. Fong PC, Boss DS, Yap TA, et al., Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009; 361: 123-134.
60. Edwards SL, Brough R, Lord CJ, et al., Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008; 451: 1111-1115.
61. Showalter SL, Charles S, Belin J, et al., 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.
62. James E, Waldron-Lynch MG, Saif MW,. Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature. Anticancer Drugs 2009; 20: 634-638.
63. Chalasani P, Kurtin S, Dragovich T,. Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation. Jop 2008; 9: 305-308.
64. Sakai W, Swisher EM, Karlan BY, et al., Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 2008; 451: 1116-1120.
65. Hucl T, Rago C, Gallmeier E, et al., A syngeneic variance library (SyVaL) for functional annotation of human variation: application to BRCA2. Cancer Res 2008; 68: 5023-5030.
66. Gallmeier E, Calhoun ES, Rago C, et al., Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model of specific therapeutic options. Gastroenterology 2006; 130: 2145-2154.
67. Abbott DW, Freeman ML, Holt JT,. Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 1998; 90: 978-985.
68. Wiegant WW, Overmeer RM, Godthelp BC, et al., Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function. Mutat Res 2006; 600: 79-88.
69. Treszezamsky AD, Kachnic LA, Feng Z, et al., BRCA1- and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase II. Cancer Res 2007; 67: 7078-7081.
70. Bollag G, Hirth P, Tsai J, et al., Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010; 467: 596-599.
71. Halaban R, Zhang W, Bacchiocchi A, et al., PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res; 23: 190-200.
72. Schonleben F, Qiu W, Ciau NT, et al., PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res 2006; 12: 3851-3855.
73. Nyman DW, Campbell KJ, Hersh E, et al., Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. J Clin Oncol 2005; 23: 7785-7793.
74. Sato N, Fukushima N, Maehara N, et al., SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene 2003; 22: 5021-5030.
75. Desai NP, Trieu V, Hwang LY, et al., Improved effectiveness of nanoparticle albumin-bound (nab) paclitaxel versus polysorbate-based docetaxel in multiple xenografts as a function of HER2 and SPARC status. Anticancer Drugs 2008; 19: 899-909.
76. Wang TL, Diaz LA, Jr., Romans K, et al., Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proc Natl Acad Sci USA 2004; 101: 3089-3094; Epub17 February 2004.
77. Carethers JM, Smith EJ, Behling CA, et al., Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 2004; 126: 394-401.
78. Berman DM, Karhadkar SS, Maitra A, et al., Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425: 846-851.
79. Gorre ME, Mohammed M, Ellwood K, et al., Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876-880.
80. Wakai T, Kanda T, Hirota S, et al., Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Br J Cancer 2004; 90: 2059-2061.
81. Sinha BK,. Topoisomerase inhibitors. A review of their therapeutic potential in cancer. Drugs 1995; 49: 11-19.
82. Hucl T, Gallmeier E, Kern SE,. Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials. Cell Cycle 2007; 6: 1336-1341.
83. Diehl F, Li M, Dressman D, et al., Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA 2005; 102: 16368-16373.
84. Li M, Chen WD, Papadopoulos N, et al., Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol 2009; 27: 858-863.
85. Leary RJ, Kinde I, Diehl F, et al., Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med 2010; 2: 20ra14.