Identifying pancreatic cancer patients for targeted treatment: The challenges and limitations of the current selection process and vision for the future

Expert Opinion on Drug Delivery

Volumn 7, Issue 3, 2010, Pages 273-284

  Showalter, Shayna L ^a   Charles, Sarah ^b   Belin, Justin ^b   Cozzitorto, Joseph ^a   Einstein, Peter ^d   Richards, Nathan G ^a   Sauter, Patricia K ^a   Kennedy, Eugene P ^a   Witkiewicz, Agnes ^a,b,c   Brody, Jonathan R ^a,c   Yeo, Charles J ^a,c  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d NONE

Author keywords

BRCA2; Familial pancreatic cancer; Fanconi anemia; Interstrand crosslinking agents; Pancreatic ductal adenocarcinoma; PARP inhibitors

Indexed keywords

BRCA2 PROTEIN; CAPECITABINE; CHLORAMBUCIL; CISPLATIN; GEMCITABINE; MELPHALAN; MITOMYCIN C; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR;

APC GENE; BREAST CANCER; CANCER RADIOTHERAPY; CANCER SUSCEPTIBILITY; CASE REPORT; CDKN2A GENE; CFTR GENE; CTRC GENE; CYSTIC FIBROSIS; DNA REPAIR; DRUG TARGETING; FAMILIAL ATYPICAL MULTIPLE MOLE MELANOMA SYNDROME; FAMILIAL CANCER; FAMILIAL COLON POLYPOSIS; FANCONI ANEMIA; FEMALE; FRAMESHIFT MUTATION; GENE; GENETIC PREDISPOSITION; HUMAN; JEW; MLH1 GENE; MSH2 GENE; MSH6 GENE; ONCOGENE; OVARY CANCER; P16 GENE; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PANCREAS RESECTION; PATIENT SELECTION; PEDIGREE; PEUTZ JEGHERS SYNDROME; PMS2 GENE; PRSS1 GENE; REVIEW; SPINK1 GENE; SPLENECTOMY; STK11 GENE; TREATMENT PLANNING; TUMOR SUPPRESSOR GENE;

ANTINEOPLASTIC AGENTS; DRUG DELIVERY SYSTEMS; FRAMESHIFT MUTATION; HUMANS; PANCREATIC NEOPLASMS; PATIENT SELECTION;

EID: 77749283334     PISSN: 17425247     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425240903544462     Document Type: Review

References (70)

1. Kleeff J, Michalski CW, Friess H, Buchler MW. Surgical treatment of pancreatic cancer: the role of adjuvant and multimodal therapies. Eur J Surg Oncol 2007;33(7):817-23
2. Bilimoria KY, Bentrem DJ, Ko CY, et al. National failure to operate on early stage pancreatic cancer. Ann Surg 2007;246(2):173-80
3. Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg 1999;189(1):1-7
4. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321(5897):1801-6
5. Jones S, Hruban RH, Kamiyama M, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009;324(5924):217
6. Tersmette AC, Petersen GM, Offerhaus GJ, et al. Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 2001;7(3):738-44
7. Wang W, Chen S, Brune KA, et al. PancPRO: risk assessment for individuals with a family history of pancreatic cancer. J Clin Oncol 2007;25(11):1417-22
8. Mathew CG. Fanconi anaemia genes and susceptibility to cancer. Oncogene 2006;25(43):5875-84
9. Shah NP. Bench to bedside: BRCA: from therapeutic target to therapeutic shield. Nat Med 2008;14(5):495-6
10. Lux MP, Fasching PA, Beckmann MW. Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med 2006;84(1):16-28
11. Windsor JA. An update on familial pancreatic cancer and the management of asymptomatic relatives. HPB (Oxford) 2007;9(1):4-7
12. Couch FJ, Johnson MR, Rabe KG, et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2007;16(2):342-6
13. Figer A, Irmin L, Geva R, et al. The rate of the 6174delT founder Jewish mutation in BRCA2 in patients with non-colonic gastrointestinal tract tumours in Israel. Br J Cancer 2001;84(4):478-81
14. Goggins M, Schutte M, Lu J, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996;56(23):5360-4
15. Hahn SA, Greenhalf B, Ellis I, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 2003;95(3):214-21
16. 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(13):3789-93
17. van der Heijden MS, Brody JR, Gallmeier E, et al. Functional defects in the fanconi anemia pathway in pancreatic cancer cells. Am J Pathol 2004;165(2):651-7
18. van der Heijden MS, Yeo CJ, Hruban RH, Kern SE. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res 2003;63(10):2585-8
19. Soegaard M, Kjaer SK, Cox M, et al. BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin Cancer Res 2008;14(12):3761-7
20. Brozek I, Ochman K, Debniak J, et al. High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland. Gynecol Oncol 2008;108(2):433-7
21. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 2005;104(12):2807-16
22. Risch HA, McLaughlin JR, Cole DE, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 2001;68(3):700-10
23. Garcia MJ, Benitez J. The Fanconi anaemia/BRCA pathway and cancer susceptibility. Searching for new therapeutic targets. Clin Transl Oncol 2008;10(2):78-84
24. Gallmeier E, Calhoun ES, Rago C, et al. Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options. Gastroenterology 2006;130(7):2145-54
25. van der Heijden MS, Brody JR, Dezentje DA, et al. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res 2005;11(20):7508-15
26. 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(2):123-34
27. Donawho CK, Luo Y, Penning TD, et al. ABT-888, an orally active poly (ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 2007;13(9):2728-37
28. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434(7035):917-21
29. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly (ADP-ribose) polymerase. Nature 2005;434(7035):913-7
30. McCabe N, Turner NC, Lord CJ, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 2006;66(16):8109-15
31. Roumiantsev S, Shah NP, Gorre ME, et al. Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc Natl Acad Sci USA 2002;99(16):10700-5
32. Edwards SL, Brough R, Lord CJ, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008;451(7182):1111-5
33. Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 2008;451(7182):1116-20
34. Brody JR, Costantino CL, Potoczek M, et al. Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma. Mod Pathol 2009;22(5):651-9
35. Evans DG, Neuhausen SL, Bulman M, et al. Haplotype and cancer risk analysis of two common mutations, BRCA1 4184del4 and BRCA2 2157delG, in high risk northwest England breast/ovarian families. J Med Genet 2004;41(2):e21
36. Mavraki E, Gray IC, Bishop DT, Spurr NK. Germline BRCA2 mutations in men with breast cancer. Br J Cancer 1997;76(11):1428-31
37. Yeo TP, Hruban RH, Brody J, et al. Assessment of "Gene- Environment" interaction in cases of familial and sporadic pancreatic cancer. J Gastrointest Surg 2009;13(8):1487-94
38. Showalter SL, Showalter TN, Witkiewicz A, et al. Evaluating the drug-target relationship between thymidylate synthase expression and tumor response to 5-fluorouracil: is it time to move forward? Cancer Biol Ther 2008;7(7):1584-90
39. Gallmeier E, Hucl T, Calhoun ES, et al. Gene-specific selection against experimental fanconi anemia gene inactivation in human cancer. Cancer Biol Ther 2007;6(5):654-60
40. Gallmeier E, Kern SE. Targeting fanconi anemia/BRCA2 pathway defects in cancer: the significance of preclinical pharmacogenomic models. Clin Cancer Res 2007;13(1):4-10
41. Hucl T, Rago C, Gallmeier E, et al. A syngeneic variance library for functional annotation of human variation: application to BRCA2. Cancer Res 2008;68(13):5023-30
42. Ashworth A. Drug resistance caused by reversion mutation. Cancer Res 2008;68(24):10021-3
43. Ashworth A. 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(22):3785-90
44. 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(6):766-81; quiz 665
45. Brand RE, Lerch MM, Rubinstein WS, et al. Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 2007;56(10):1460-9
46. Steinberg WM, Barkin JS, Bradley EL III, et al. Should patients with a strong family history of pancreatic cancer be screened on a periodic basis for cancer of the pancreas? Pancreas 2009;38(5):e137-50
47. Canto MI, Goggins M, Yeo CJ, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol 2004;2(7):606-21
48. Brentnall TA, Bronner MP, Byrd DR, et al. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 1999;131(4):247-55
49. Rulyak SJ, Brentnall TA. Inherited pancreatic cancer: surveillance and treatment strategies for affected families. Pancreatology 2001;1(5):477-85
50. Kimmey MB, Bronner MP, Byrd DR, Brentnall TA. Screening and surveillance for hereditary pancreatic cancer. Gastrointest Endosc 2002;56(4 Suppl):S82-6
51. McFaul CD, Greenhalf W, Earl J, et al. Anticipation in familial pancreatic cancer. Gut 2006;55(2):252-8
52. Neglia JP, FitzSimmons SC, Maisonneuve P, et al. The risk of cancer among patients with cystic fibrosis. Cystic Fibrosis and Cancer Study Group. N Engl J Med 1995;332(8):494-9
53. Fernandez E, La Vecchia C, Porta M, et al. Pancreatitis and the risk of pancreatic cancer. Pancreas 1995;11(2):185-9
54. Mendes-Pereira AM MS, Brough R, McCarthy A, et al. A Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 2009;1:315-22
55. 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(3):305-8
56. Thompson D, Easton DF. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002;94(18):1358-65
57. Giardiello FM, Welsh SB, Hamilton SR, et al. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 1987;316(24):1511-4
58. Giardiello FM, Brensinger JD, Tersmette AC, et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119(6):1447-53
59. 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(6):1835-40
60. Ellis I, Lerch MM, Whitcomb DC. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues. Pancreatology 2001;1(5):405-15
61. 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):442-6
62. Howes N, Lerch MM, Greenhalf W, et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2004;2(3):252-61
63. Rozenblum E, Schutte M, Goggins M, et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res 1997;57(9):1731-4
64. Nakata B, Wang YQ, Yashiro M, et al. Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res 2002;8(8):2536-40
65. Giardiello FM, Offerhaus GJ, Lee DH, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 1993;34(10):1394-6
66. Burt RW. Colon cancer screening. Gastroenterology 2000;119(3):837-53
67. Wallace MH, Phillips RK. Upper gastrointestinal disease in patients with familial adenomatous polyposis. Br J Surg 1998;85(6):742-50
68. Krysa J, Steger A. Pancreas and cystic fibrosis: the implications of increased survival in cystic fibrosis. Pancreatology 2007;7(5-6):447-50
69. Maisonneuve P, Marshall BC, Lowenfels AB. Risk of pancreatic cancer in patients with cystic fibrosis. Gut 2007;56(9):1327-8
70. Singh AP, Chauhan SC, Andrianifahanana M, et al. MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms. Oncogene 2007;26(1):30-41