EGFR and Cytoplasmic Kinase Src Targeting in Pancreatic Cancer

  • Vidya Mukhund
  • Afroz Alam
  • Ganji Purnachandra NagarajuEmail author


Pancreatic cancer (PC) is one of the most devastating malignancies in the world and the fourth leading cause of fatalities associated with cancer in the United States. PC has an extremely poor prognosis and a 5-year survival rate ranging between 1% and 5%. In emerging PC treatment, tyrosine kinases and its inhibitors signify a new generation of therapeutic drugs that specifically target tumor pathways that are associated with tumorigenesis such as cell cycle mechanism, signal transduction, apoptosis, and angiogenesis. Tyrosine kinases such as EGF and Src kinases were specifically used to target PC progression and metastasis. In this chapter, we discuss the EGFR and Src role in progression PC.


Pancreatic cancer Progression Metastasis EGFR Src 


  1. 1.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30CrossRefGoogle Scholar
  2. 2.
    Casalini P et al (2004) Role of HER receptors family in development and differentiation. J Cell Physiol 200(3):343–350CrossRefGoogle Scholar
  3. 3.
    Alexandrov LB et al (2013) Signatures of mutational processes in human cancer. Nature 500(7463):415CrossRefGoogle Scholar
  4. 4.
    Neoptolemos JP et al (2001) Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg 234(6):758CrossRefGoogle Scholar
  5. 5.
    Inoue S, Tezel E, Nakao A (2001) Molecular diagnosis of pancreatic cancer. Hepato-Gastroenterology 48(40):933–938PubMedGoogle Scholar
  6. 6.
    Dongbin L et al (2010) Intraductal papillary mucinous neoplasms of the pancreas: diagnosis and management. Eur J Gastroenterol Hepatol 22(9):1029–1038CrossRefGoogle Scholar
  7. 7.
    Hingorani SR et al (2003) Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4(6):437–450CrossRefGoogle Scholar
  8. 8.
    Handra-Luca A et al (2014) EGFR expression in pancreatic adenocarcinoma. Relationship to tumour morphology and cell adhesion proteins. J Clin Pathol 67(4):295–300CrossRefGoogle Scholar
  9. 9.
    Smit VT et al (1988) KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 16(16):7773–7782CrossRefGoogle Scholar
  10. 10.
    Brennan PJ et al (2002) HER2/Neu: mechanisms of dimerization/oligomerization. Oncogene 21(2):328CrossRefGoogle Scholar
  11. 11.
    Seshacharyulu P et al (2012) Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 16(1):15–31CrossRefGoogle Scholar
  12. 12.
    Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438(7070):967–974CrossRefGoogle Scholar
  13. 13.
    De Luca A et al (2008) The role of the EGFR signaling in tumor microenvironment. J Cell Physiol 214(3):559–567CrossRefGoogle Scholar
  14. 14.
    Day JD et al (1996) Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms. Hum Pathol 27(2):119–124CrossRefGoogle Scholar
  15. 15.
    Jhappan C et al (1990) TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61(6):1137–1146CrossRefGoogle Scholar
  16. 16.
    Uegaki K et al (1997) Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res 17(5B):3841–3847PubMedGoogle Scholar
  17. 17.
    Bloomston M et al (2006) Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg 23(1–2):74–79CrossRefGoogle Scholar
  18. 18.
    Lei S et al (1995) Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival. Int J Gastrointest Cancer 17(1):15–21Google Scholar
  19. 19.
    Komoto M et al (2009) HER2 overexpression correlates with survival after curative resection of pancreatic cancer. Cancer Sci 100(7):1243–1247CrossRefGoogle Scholar
  20. 20.
    Ocana A et al (2012) HER3 overexpression and survival in solid tumors: a meta-analysis. JNCI: J Natl Cancer Inst 105(4):266–273CrossRefGoogle Scholar
  21. 21.
    Graber HU et al (1999) ErbB-4 mRNA expression is decreased in non-metastatic pancreatic cancer. Int J Cancer 84(1):24–27CrossRefGoogle Scholar
  22. 22.
    Thybusch-Bernhardt A, Beckmann S, Juhl H (2001) Comparative analysis of the EGF-receptor family in pancreatic cancer: expression of HER-4 correlates with a favourable tumor stage. Int J Surg Investig 2(5):393–400PubMedGoogle Scholar
  23. 23.
    Cook N, Frese K, Moore M (2014) Assessing the role of the EGF receptor in the development and progression of pancreatic cancer. Gastrointest Cancer: Targets Ther 4:23–37Google Scholar
  24. 24.
    Korc Ma et al (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Investig 90(4):1352CrossRefGoogle Scholar
  25. 25.
    Bromann PA, Korkaya H, Courtneidge SA (2004) The interplay between Src family kinases and receptor tyrosine kinases. Oncogene 23(48):7957–7968CrossRefGoogle Scholar
  26. 26.
    Ishizawar R, Parsons SJ (2004) c-Src and cooperating partners in human cancer. Cancer Cell 6(3):209–214CrossRefGoogle Scholar
  27. 27.
    Nagaraj NS, Washington MK, Merchant NB (2011) Combined blockade of Src kinase and epidermal growth factor receptor with gemcitabine overcomes STAT3-mediated resistance of inhibition of pancreatic tumor growth. Clin Cancer Res 17(3):483–493CrossRefGoogle Scholar
  28. 28.
    Mendelsohn J, Baselga J (2006) Epidermal growth factor receptor targeting in cancer. Semin Oncol 33:369–385 ElsevierCrossRefGoogle Scholar
  29. 29.
    Mendelsohn J, Baselga J (2000) The EGF receptor family as targets for cancer therapy. Oncogene 19(56):6550CrossRefGoogle Scholar
  30. 30.
    Olayioye MA et al (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19(13):3159–3167CrossRefGoogle Scholar
  31. 31.
    Boonstra J et al (1995) The epidermal growth factor. Cell Biol Int 19(5):413–430CrossRefGoogle Scholar
  32. 32.
    Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21(14):2787–2799CrossRefGoogle Scholar
  33. 33.
    Tzeng C-WD et al (2007) Pancreatic cancer epidermal growth factor receptor (EGFR) intron 1 polymorphism influences postoperative patient survival and in vitro erlotinib response. Ann Surg Oncol 14(7):2150–2158CrossRefGoogle Scholar
  34. 34.
    Moore MJ et al (2007) 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 25(15):1960–1966CrossRefGoogle Scholar
  35. 35.
    Jaganathan S, Yue P, Turkson J (2010) Enhanced sensitivity of pancreatic cancer cells to concurrent inhibition of aberrant signal transducer and activator of transcription 3 and epidermal growth factor receptor or Src. J Pharmacol Exp Ther 333(2):373–381CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Vidya Mukhund
    • 1
  • Afroz Alam
    • 1
  • Ganji Purnachandra Nagaraju
    • 2
    Email author
  1. 1.Department of Bioscience and BiotechnologyBanasthali UniversityBanasthaliIndia
  2. 2.Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer InstituteEmory UniversityAtlantaUSA

Personalised recommendations