Pancreatic cancer

Česká verzia

Authors: T. Hucl
Authors place of work: Klinika hepatogastroenterologie IKEM, Praha
Published in the journal: Gastroent Hepatol 2012; 66(5): 350-356
Category: Gastrointestinal Oncology: Review Article

Summary

Pancreatic cancer is a disease showing increasing frequency and a devastating prognosis. Despite advances in knowledge of its biology and treatment, less than 5% of patients survive for more than 5 years. This illness is most frequently sporadic, without a known, dominant cause. The main risk factors for its development include smoking, obesity with an excessive consumption of fats, advanced age, male gender, ethnic origin, chronic pancreatitis or diabetes mellitus. Less frequently, carcinoma of the pancreas has a hereditary cause, be it as part of certain genetic syndromes or without any previously known specific genetic predisposition. Similarly to other epithelial tumours, carcinoma of the pancreas develops through gradual progression from non-invasive precursors, some of which can be identified using imaging methods. The histological progress of these precursors follows genetic progression, which forms the substance of the pathogenesis of the illness. DNA damage, or other, non-genetic, changes, leads to the alteration of cellular signalling pathways resulting in changes in the biological behaviour of the cells and initiation, progression and metastasizing of the disease. The main causes of the unfavourable prognosis are the early generalisation of the disease and its resistance to chemotherapy and radiotherapy. Patients with localised disease of the disease are indicated for surgical intervention followed by adjuvant chemotherapy. Locally advanced or generalised tumours are suitable for palliative chemotherapy or chemoradiotherapy. Neoadjuvant therapy is now gaining status within the therapeutic algorithm. A closer understanding of the molecular mechanisms of pathogenesis and the possibility of their influencing through targeted anti-tumour treatment, however, represent the greatest potential for the treatment of carcinoma of the pancreas.

Key words:
pancreatic neoplasms – ethiology – signalling pathway – therapy

The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
20. 9. 2012

Accepted:
4. 10. 2012

Zdroje

1. Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol 2006; 20(2): 197–209.

2. Saglova A, Spicak J, Hucl T. Karcinom pankreatu: Molekulární biologie a časná diagnostika. Prak Lék 2010; 90: 489–493.

3. Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol 2009; 6(12): 699–708.

4. Chari ST, Leibson CL, Rabe KG et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008; 134(1): 95–101.

5. Almoguera C, Shibata D, Forrester K et al. Most human carcinomas of the exocrine pancreas contain mutant c-Kras genes. Cell 1988; 53(4): 549–554.

6. Caldas C, Hahn SA, da Costa LT et al. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 1994; 8(1): 27–32.

7. Schutte M, Hruban RH, Geradts J et al. Abrogation of the Rb/p16 tumor-supressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997; 57(15): 3126–3130.

8. Hanh SA, Schutte M, Hoque AT et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996; 271(5247): 350–353.

9. Goggins M, Shekher M, Turnacioglu K et al. Genetic alterations of the TGF beta receptor genes in pancreatic and biliary adenocarcinomas. Cancer Res 1998; 58(23): 5329–5332.

10. Hucl T. Molekulární patogeneze karcinomu pankreatu. Čes a Slov Ganstroent a Hepatol 2009; 63(2): 58–64.

11. Jones S, Zhang X, Parsons DW et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321(5897): 1801–1806.

12. Hucl T, Brody JR, Gallmeir E et al. High cancer-specific expression of mesothelin (MSLN) is attributable to an upstream enhancer containing a transcription enhancer factor dependent MCAT motif. Cancer Res 2007; 67(19): 9055–9065.

13. Zavoral M, Minarikova P, Zavada F et al. Molecular biology of pancreatic cancer. World J Gastroenterol 2011; 17(24): 2897–2908.

14. Vincent A, Herman J, Schulick R et al. Pancreatic cancer. Lancet 2011; 378(9791): 607–620.

15. 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(5933): 1457–1461.

16. Thomas AM, Santarsiero LM, Lutz ER et al. Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 2004; 200(3): 297–306.

17. Kern SE, Shibata D. The fuzzy math of solid tumor stem cells. Cancer Res 2007; 67(19): 8985–8988.

18. Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med 2009; 361(21): 2094–2096.

19. Yachida S, Jones S, Bozic I et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010; 467(7319): 1114–1117.

20. Hruban RH, Adsaz NV, Albores-Saavedra J et al. Pancreatic intraepithelial neoplasia: A new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 2001; 25(5): 579–586.

21. Hruban RH, Maitra A, Kern SE et al. Precursors to pancreatic cancer. Gastroenterol Clin North Am 2007; 36(4): 831–849.

22. Tanaka M, Fernandez-del Castillo C, Adsay V et al. International consensus guidelines 201 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12(3): 183–197.

23. 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): 766–781.

24. Canto MI et al. Strategies for Screening for Pancreatic Adenocarcinoma in High-Risk Patients. Semin Oncol 2007; 34(4): 295–302.

25. Oliverius M, Kala Z, Varga M et al. Radical surgery for pancreatic malignancy in the elderly. Pancreatology 2010; 10(4): 499–502.

26. Van der GaaG NA, Rauws EA, van Eijck CH et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med 2010; 362(2): 129–137.

27. Laethem JL, Verslype C, Iovanna JL et al. New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. Ann Oncol 2012; 23(3): 570–576.

28. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364(19): 1817–1825.

29. 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): 5023–5030.

30. Moore MJ, Goldstein D, Hamm J et al. 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(15): 1960–1966.