Skip to main content
SpringerLink
Log in

Pancreatic Cancer

  • Chapter
  • First Online:
Oncology in the Precision Medicine Era

Abstract

Pancreatic cancer is one of the deadliest malignancies. According to the American Cancer Society, there is an estimated 55,440 new cases of pancreatic cancer in 2018 with approximately 44,330 deaths from this disease. The 5-year relative survival rate is 8% for all stages of pancreatic cancer combined, and for the minority of patients who present with local disease, approximately 10%, the 5-year survival rate is only 32%. The majority of patients, greater than 80%, have unresectable disease with most presenting with distant disease. The 5-year survival rate in this group is a dismal 3%. This review discusses the evolution of pancreatic cancer treatment as we make advances toward precision medicine in this deadly disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. American Cancer Society. Cancer facts & figures 2018. Atlanta: American Cancer Society; 2018.

    Google Scholar 

  2. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21.

    Article  CAS  PubMed  Google Scholar 

  3. Burris HA 3rd, Moore MJ, Andersen J, 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(6):2403–13.

    Article  CAS  PubMed  Google Scholar 

  4. 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):1960–6.

    Article  CAS  PubMed  Google Scholar 

  5. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.

    Article  CAS  PubMed  Google Scholar 

  6. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.

    Article  CAS  Google Scholar 

  7. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998–2006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular profiling of pancreatic cancer patients: initial results from the know your tumor initiative. Clin Cancer Res. 2018;24:5018–27.

    Google Scholar 

  9. Aguirre AJ, Nowak JA, Camarda ND, et al. Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine. Cancer Discov. 2018;8(9):1096–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53(4):549–54.

    Article  CAS  PubMed  Google Scholar 

  12. Fitzgerald TL, Lertpiriyapong K, Cocco L, et al. Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells. Advances in biological regulation. 2015;59:65–81.

    Article  CAS  PubMed  Google Scholar 

  13. Ardito CM, Gruner BM, Takeuchi KK, et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell. 2012;22(3):304–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Siveke JT, Crawford HC. KRAS above and beyond - EGFR in pancreatic cancer. Oncotarget. 2012;3(11):1262–3.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Oliveira-Cunha M, Newman WG, Siriwardena AK. Epidermal growth factor receptor in pancreatic cancer. Cancers. 2011;3(2):1513–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang M, Anand S, Murphy EA, et al. EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation. Oncogene. 2012;31(22):2783–93.

    Article  CAS  PubMed  Google Scholar 

  17. Waddell N, Pajic M, Patch AM, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518(7540):495–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Manji GA, Olive KP, Saenger YM, Oberstein P. Current and emerging therapies in metastatic pancreatic cancer. Clin Cancer Res. 2017;23(7):1670–8.

    Article  PubMed  Google Scholar 

  19. Lowery MA, Jordan EJ, Basturk O, et al. Real-time genomic profiling of pancreatic ductal adenocarcinoma: potential actionability and correlation with clinical phenotype. Clin Cancer Res. 2017;23(20):6094–100.

    Article  CAS  PubMed  Google Scholar 

  20. Moffitt RA, Marayati R, Flate EL, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gore J, Korc M. Pancreatic cancer stroma: friend or foe? Cancer Cell. 2014;25(6):711–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67(19):9518–27.

    Article  CAS  PubMed  Google Scholar 

  23. Bai Y, Bai Y, Dong J, et al. Hedgehog signaling in pancreatic fibrosis and cancer. Medicine. 2016;95(10):e2996.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Amanam I, Chung V. Targeted therapies for pancreatic cancer. Cancers. 2018;10(2):36.

    Article  PubMed Central  CAS  Google Scholar 

  25. Philip PA, Benedetti J, Corless CL, et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010;28(22):3605–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Philip PA, Goldman B, Ramanathan RK, et al. Dual blockade of epidermal growth factor receptor and insulin-like growth factor receptor-1 signaling in metastatic pancreatic cancer: phase Ib and randomized phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus erlotinib (SWOG S0727). Cancer. 2014;120(19):2980–5.

    Article  CAS  PubMed  Google Scholar 

  27. Schultheis B, Reuter D, Ebert MP, et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study. Ann Oncol. 2017;28(10):2429–35.

    Article  CAS  PubMed  Google Scholar 

  28. Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol. 2018;36(4):359–66.

    Article  CAS  PubMed  Google Scholar 

  29. Kindler HL, Niedzwiecki D, Hollis D, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010;28(22):3617–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Catenacci DV, Junttila MR, Karrison T, et al. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015;33(36):4284–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. SEC filing and press release dated 27 Jan 2012.

    Google Scholar 

  32. Ko AH, LoConte N, Tempero MA, et al. A phase I study of FOLFIRINOX plus IPI-926, a hedgehog pathway inhibitor, for advanced pancreatic adenocarcinoma. Pancreas. 2016;45(3):370–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lee JJ, Perera RM, Wang H, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014;111(30):E3091–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Smith DC, Eisenberg PD, Manikhas G, et al. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res. 2014;20(24):6295–303.

    Article  CAS  PubMed  Google Scholar 

  35. Hurwitz H, Van Cutsem E, Bendell J, et al. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Investig New Drugs. 2018;36:683.

    Article  CAS  Google Scholar 

  36. Van Cutsem E, van de Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol. 2004;22(8):1430–8.

    Article  PubMed  CAS  Google Scholar 

  37. Chung V, McDonough S, Philip PA, et al. Effect of selumetinib and MK-2206 vs oxaliplatin and fluorouracil in patients with metastatic pancreatic cancer after prior therapy: SWOG S1115 study randomized clinical trial. JAMA Oncol. 2017;3(4):516–22.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bustinza-Linares E, Kurzrock R, Tsimberidou AM. Salirasib in the treatment of pancreatic cancer. Future Oncol (London, England). 2010;6(6):885–91.

    Article  CAS  Google Scholar 

  39. Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed. 2005;7(2):60.

    PubMed  PubMed Central  Google Scholar 

  40. Lynch HT, Deters CA, Snyder CL, et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005;158(2):119–25.

    Article  CAS  PubMed  Google Scholar 

  41. O'Reilly EM, Lee JW, Lowery MA, et al. Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma. Cancer. 2018;124(7):1374–82.

    Article  CAS  PubMed  Google Scholar 

  42. Morton LM, Dores GM, Tucker MA, et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008. Blood. 2013;121(15):2996–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade Science. 2017;357(6349):409–13.

    CAS  PubMed  Google Scholar 

  44. US Food and Drug Administration: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. 2017.

    Google Scholar 

  45. Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(24):2545–56.

    Article  PubMed  Google Scholar 

  46. Hu ZI, Shia J, Stadler ZK, et al. Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations. Clin Cancer Res. 2018;24(6):1326–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA, USA

    Addie Hill & Vincent Chung

Authors
  1. Addie Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent Chung .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    Ravi Salgia

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hill, A., Chung, V. (2020). Pancreatic Cancer. In: Salgia, R. (eds) Oncology in the Precision Medicine Era. Springer, Cham. https://doi.org/10.1007/978-3-030-31471-2_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-31471-2_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-31470-5

  • Online ISBN: 978-3-030-31471-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation