BRCA and Pancreatic Cancer
Abstract
Germline mutations in BRCA genes have been associated with pancreatic cancer. Laboratory and clinical data suggest that patients with BRCA mutations may be more responsive to therapy consisting of conventional chemotherapy with a poly(ADP-ribose) polymerase inhibitor (PARPi). The most recent data from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting will be reviewed (Abstracts #11024 and #TPS4144).
Image: Effect of PARP, BRCA and PARP inhibition on DNA replication.
Downloads
References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan; 63(1):11-30.
Narod SA, Foulkes WD. Brca1 and brca2: 1994 and beyond. Nat Rev Cancer 2004;4:665-76.
Cancer risks in brca2 mutation carriers. The breast cancer linkage consortium. J Natl Cancer Inst 1999;91:1310-6.
Murphy KM, Brune KA, Griffin C, Sollenberger JE, Petersen GM, Bansal R, et al. Evaluation of candidate genes map2k4, madh4, acvr1b, and brca2 in familial pancreatic cancer: Deleterious brca2 mutations in 17%. Cancer Res 2002;62:3789-93.
J Iqbal, A Ragone, J Lubinski, HT Lynch, P Moller, P Ghadirian, WD Foulkes, S Armel, A Eisen, SL Neuhausen, L Senter, CF Singer, P Ainsworth, C Kim-Sing, N Tung, E Friedm. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. British Journal of Cancer (2012); 107(12):2005-2009.
Yuan SS, Lee SY, Chen G, Song M, Tomlinson GE, Lee EY. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res. 1999;59(15):3547-51.
van der Heijden MS, Brody JR, Dezentje DA, Gallmeier E, Cunningham SC, Swartz MJ, DeMarzo AM, Offerhaus GJ, Isacoff WH, Hruban RH, Kern SE. In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005;11(20):7508-15.
McCabe N, Lord CJ, Tutt AN, Martin NM, Smith GC, Ashworth A. Brca2-deficient capan-1 cells are extremely sensitive to the inhibition of poly (adp-ribose) polymerase: An issue of potency. Cancer Biol Ther 2005;4:934-36.
Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in brca mutant cells as a therapeutic strategy. Nature 2005;434:917-21.
Fong PC, Boss DS, Yap TA, Tutt A, Wu PJ, Mergui-Roelvink M, et al. Inhibition of poly(adp-ribose) polymerase in tumors from brca mutation carriers. New Engl J Med 2009;361:123-34.
Slater EP, Langer P, Niemczyk E, Strauch K, Butler J, Habbe N, Neoptolemos JP, Greenhalf W, Bartsch DK. PALB2 mutations in European familial pancreatic cancer families. Clin Genet 2010 Nov;78(5):490-4.
Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 2006;22(6):719-29.
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 Aug;20(7): 634-8
Tran B MS, Zogopoulos G, Borgida A, Holter S, Gallinger S et al. Platinum-based chemotherapy (pt-chemo) in pancreatic adenocarcinoma (pc) associated with brca mutations: A translational case series. J Clin Oncol 2012;30:Abstract 217.
Lowery MA, Kelsen DP, Stadler ZK, Yu KH, Janjigian YY, Ludwig E, et al. An emerging entity: Pancreatic adenocarcinoma associated with a known brca mutation: Clinical descriptors, treatment implications, and future directions. Oncologist 2011;16:1397-402.
Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation: An open-label phase II study. J Clin Oncol 31, 2013 (ASCO 2013 suppl; abstr 11024).
O’Reilly EM, Lowery M, Yu K, Capanu M, Stadler Z, Epstein A, Golan T, Segal A, Segal M, Salo-Mullen E, Tang L, Hollywood E, Moynahan M, Do K, Moore M, Kindler H, Mayer R, Chen A, Kelsen D. Randomized phase II study of gemcitabine (G), cisplatin (C) with or without veliparib (V) (arms A, B) and a phase II single-arm study of single-agent veliparib (arm C) in patients with BRCA or PALB2-mutated pancreas adenocarcinoma (PC). J Clin Oncol 31, 2013 (ASCO 2013 suppl; abstr TPS4144).
Copyright (c) 2014 Gregory T Brennan, Valerie Relias, Muhammad Wasif Saif
This work is licensed under a Creative Commons Attribution 4.0 International License.
As a member of Publisher International Linking Association, PILA, iMedPub Group’s JOP follows the Creative Commons Attribution License and Scholars Open Access publishing policies. Journal of the Pancreas is the Council Contributor Member of Council of Science Editors (CSE) and following the CSE slogan Education, Ethics, and Evidence for Editors.