Genetic Factors Affecting Patient Responses to Pancreatic Cancer Treatment

Overview

Journal Ann Gastroenterol

Specialty Gastroenterology

Date 2016 Oct 7

PMID 27708512

Citations 4

Authors

George Fotopoulos

Konstantinos Syrigos

Muhammad Wasif Saif

Affiliations

Soon will be listed here.

Abstract

Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies.

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References

Wright G, Chesla D, Chung M . Using next-generation sequencing to determine potential molecularly guided therapy options for patients with resectable pancreatic adenocarcinoma. Am J Surg. 2016; 211(3):506-11. DOI: 10.1016/j.amjsurg.2015.11.002. View

Aguirre A, Bardeesy N, Sinha M, Lopez L, Tuveson D, Horner J . Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 2003; 17(24):3112-26. PMC: 305262. DOI: 10.1101/gad.1158703. View

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K . Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007; 297(3):267-77. DOI: 10.1001/jama.297.3.267. View

Poplin E, Wasan H, Rolfe L, Raponi M, Ikdahl T, Bondarenko I . Randomized, multicenter, phase II study of CO-101 versus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma: including a prospective evaluation of the role of hENT1 in gemcitabine or CO-101 sensitivity. J Clin Oncol. 2013; 31(35):4453-61. DOI: 10.1200/JCO.2013.51.0826. View

Slater E, Langer P, Niemczyk E, Strauch K, Butler J, Habbe N . PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010; 78(5):490-4. DOI: 10.1111/j.1399-0004.2010.01425.x. View

Murphy K, Brune K, Griffin C, Sollenberger J, Petersen G, Bansal R . 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. View

Redston M, Caldas C, Seymour A, Hruban R, Da Costa L, Yeo C . p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res. 1994; 54(11):3025-33. View

Hahn S, Greenhalf B, Ellis I, Sina-Frey M, Rieder H, Korte B . BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003; 95(3):214-21. DOI: 10.1093/jnci/95.3.214. View

Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal I, Paraf F, Lauricella C . KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer. 2013; 133(5):1259-65. DOI: 10.1002/ijc.28106. View

10.

Blackford A, Serrano O, Wolfgang C, Parmigiani G, Jones S, Zhang X . SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009; 15(14):4674-9. PMC: 2819274. DOI: 10.1158/1078-0432.CCR-09-0227. View

11.

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y . FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364(19):1817-25. DOI: 10.1056/NEJMoa1011923. View

12.

Tobita K, Kijima H, Dowaki S, Kashiwagi H, Ohtani Y, Oida Y . Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis. Int J Mol Med. 2003; 11(3):305-9. View

13.

Moskaluk C, Hruban R, Kern S . p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997; 57(11):2140-3. View

14.

Hruban R, van Mansfeld A, Offerhaus G, van Weering D, Allison D, Goodman S . K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol. 1993; 143(2):545-54. PMC: 1887038. View

15.

Sebastiani V, Ricci F, Rubio-Viqueira B, Rubio-Viquiera B, Kulesza P, Yeo C . Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res. 2006; 12(8):2492-7. PMC: 3619210. DOI: 10.1158/1078-0432.CCR-05-2655. View

16.

Hosein P, de Lima Lopes Jr G, Pastorini V, Gomez C, Macintyre J, Zayas G . A phase II trial of nab-Paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2012; 36(2):151-6. DOI: 10.1097/COC.0b013e3182436e8c. View

17.

Hruban R, Petersen G, Ha P, Kern S . Genetics of pancreatic cancer. From genes to families. Surg Oncol Clin N Am. 1998; 7(1):1-23. View

18.

Su G, Hruban R, Bansal R, Bova G, Tang D, Shekher M . Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol. 1999; 154(6):1835-40. PMC: 1866632. DOI: 10.1016/S0002-9440(10)65440-5. View

19.

Boyle P, Hsieh C, Maisonneuve P, La Vecchia C, Macfarlane G, Walker A . Epidemiology of pancreas cancer (1988). Int J Pancreatol. 1989; 5(4):327-46. DOI: 10.1007/BF02924298. View

20.

Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schonekas H, Rost A . Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006; 24(24):3946-52. DOI: 10.1200/JCO.2005.05.1490. View