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Cell Cycle Machinery and Its Alterations in Pancreatic Cancer

  • Yusuke Kojima
  • Reeja S. Maskey
  • Yuichi J. Machida
Reference work entry

Abstract

Cancer is a disease of uncontrolled cell proliferation. Sequencing of the pancreatic cancer genome revealed frequent gene alterations that lead to constitutive proliferation signals and loss of the breaking systems. Cancer cells also display defects in the DNA repair systems, which suggest that compromised genome integrity contributes to the tumorigenesis process. These observations explain many of the abnormal behaviors of cancer cells, yet stopping proliferation of cancer cells remains a difficult task.

This chapter will describe misregulation of the cell-cycle machinery in pancreatic cancer and therapeutic options to stop abnormal proliferation. The basic concept of the normal cell cycle will be outlined first, and the mechanisms of DNA repair will be introduced. Next, alterations of the cell cycle and DNA repair systems in pancreatic cancer will be described. Finally, therapeutic opportunities to target the specific alterations in the cell cycle and DNA repair systems in pancreatic cancer will be discussed.

Keywords

Cell cycle CDK Cyclin pRB DNA damage Checkpoint p53 DNA repair BRCA 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yusuke Kojima
    • 1
  • Reeja S. Maskey
    • 1
  • Yuichi J. Machida
    • 1
  1. 1.Department of Oncology, Department of Molecular Pharmacology and Experimental TherapeuticsMayo ClinicRochesterUSA

Section editors and affiliations

  • Raul Urrutia
    • 1
  • M. W. Büchler
    • 2
  • John P. Neoptolemos
    • 3
    • 4
    • 5
  • Th. Hackert
    • 6
  1. 1.GI Research Unit, Mayo ClinicRochesterUSA
  2. 2.Department of General, Visceral and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
  3. 3.Department of SurgeryThe Royal Liverpool and Broadgreen University Hospitals NHS TrustLiverpoolUK
  4. 4.Department of Molecular and Clinical Cancer Medicine, Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK
  5. 5.NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUK
  6. 6.Department of General, Visceral and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany

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