Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2014 Mar 18.
Published in final edited form as: Cancer Cell. 2013 Mar 18;23(3):424–424.e1. doi: 10.1016/j.ccr.2013.03.008

SnapShot: Pancreatic Cancer

Haiyong Han 1, Daniel D Von Hoff 1
PMCID: PMC3638898  NIHMSID: NIHMS456880  PMID: 23518352

Pancreatic cancer can basically be divided into two major subtypes: adenocarcinoma, which is thought to arise in the exocrine portion of the pancreas (95% of cases), and rare endocrine tumors, which arise from islet cells (often designated as neuroendocrine tumors). This Snapshot concentrates on the most common and lethal type of adenocarcinoma of the pancreas: infiltrating ductal adenocarcinoma (designated here as pancreatic ductal adenocarcinoma or PDA).

Pancreatic cancer kills more than 37,000 people each year in the United States and more than 213,000 people worldwide. It has the worst 1 and 5 year survival rates of all cancers and, unfortunately, it is increasing in incidence. The highest rates of pancreatic cancer incidence are seen in industrialized and Western countries. In Europe, Nordic countries have the highest incidence rates (perhaps suggesting a role for Vitamin D). In the United States, the incidence is particularly high in Native Hawaiians, African Americans, and Korean Americans. The incidence of pancreatic cancer also increases sharply after age 50. Pancreatic cancer in young patients is frequently familial; there is a 40% increase in risk for pancreatic cancer if there is familial pancreatitis. Other risk factors include diabetes, metabolic syndrome, pancreatitis, cigarette smoking, heavy alcohol consumption, infectious agents (H. pylori, hepatitis B), and gastric resection. Diets low in fruits and vegetables and involving high intake of meat (particularly barbequed) are also associated with increased risk.

This Snapshot is designed to outline the pathology of PDA, its association with inherited cancer syndromes, information regarding the origin and evolution of the disease, clinical and molecular prognostic factors, and clinical staging along with common treatment regimens that have been proven to increase survival. Clearly, new ways to attack pancreatic cancer are needed. Also outlined in the SnapShot are four possible ways to attack the disease via genomic vulnerabilities, PDA’s fuel utilization pathways, stroma targets, and breaking immune tolerance. These include some already discovered targets as well as some additional therapeutic possibilities. We hope that this cataloging of possibilities alongside the clinical aspects of the disease will help drive new approaches and ideas for development of new therapies and new methods for early detection of this awful disease.

Acknowledgments

We would like to thank Drs. Richard Posner, Michael Barrett, Ramesh Ramanathan, and Derek Cridebring for insightful discussions during the preparation of this work. Studies in the authors’ laboratories are supported by the National Foundation for Cancer Research, Stand Up to Cancer, and the NIH/NCI (U01 CA128454).

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

References

  1. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–2413. doi: 10.1200/JCO.1997.15.6.2403. [DOI] [PubMed] [Google Scholar]
  2. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, et al. Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup . FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825. doi: 10.1056/NEJMoa1011923. [DOI] [PubMed] [Google Scholar]
  3. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin Cancer Res. 2012;18:4266–4276. doi: 10.1158/1078-0432.CCR-11-3114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7:469–483. doi: 10.1016/j.ccr.2005.04.023. [DOI] [PubMed] [Google Scholar]
  5. Iacobuzio-Donahue CA, Velculescu VE, Wolfgang CL, Hruban RH. Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing. Clin Cancer Res. 2012;18:4257–4265. doi: 10.1158/1078-0432.CCR-12-0315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jimeno A, Feldmann G, Suárez-Gauthier A, Rasheed Z, Solomon A, Zou GM, Rubio-Viqueira B, García-García E, López-Ríos F, Matsui W, et al. A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther. 2009;8:310–314. doi: 10.1158/1535-7163.MCT-08-0924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037. doi: 10.1158/0008-5472.CAN-06-2030. [DOI] [PubMed] [Google Scholar]
  8. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, et al. National Cancer Institute of Canada Clinical Trials Group . 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;25:1960–1966. doi: 10.1200/JCO.2006.07.9525. [DOI] [PubMed] [Google Scholar]
  9. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29. doi: 10.3322/caac.20138. [DOI] [PubMed] [Google Scholar]
  10. Stylianopoulos T, Martin JD, Chauhan VP, Jain SR, Diop-Frimpong B, Bardeesy N, Smith BL, Ferrone CR, Hornicek FJ, Boucher Y, et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc Natl Acad Sci USA. 2012;109:15101–15108. doi: 10.1073/pnas.1213353109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Von Hoff DD, Ervin TJ, Arena FP, Chiorean EG, Infante JR, Moore MJ, Seay TE, Tjulandin S, Ma WW, Saleh MN, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT) J Clin Oncol. 2012;30(Suppl 34):LBA148. [Google Scholar]

RESOURCES