Pancreatic Cancer pp 1613-1641 | Cite as

Emerging Therapeutic Targets in Pancreatic Adenocarcinoma

Reference work entry

Abstract

Pancreatic adenocarcinoma is one of the most lethal cancers but has limited therapeutic options necessitating continued investigation of new therapeutic agents. Recently, improved overall survival has been achieved with cytotoxic drug combinations including 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel, but the success has been modest at best. More targeted approaches focusing on EGFR and MAPK signaling have also enjoyed marginal success. Accumulating evidence suggests that pancreatic tumors have increased dependence on metabolic pathways through both KRAS and KRAS-independent mechanisms and are broadly resistant to drug therapy due to stromal remodeling. Genetic and epigenetic vulnerabilities, such as inactivating aberrations in DNA damage repair, chromatin remodeling, and microRNA dysregulation, may reveal exploitable weaknesses. Modern approaches to drug development tailored to molecularly defined subsets of patients likely to respond to targeted therapies are needed to achieve more substantial progress in this disease in an era of precision medicine.

Keywords

Pancreatic cancer Emerging therapeutics Metabolic targets DNA damage repair Chromatin remodeling Epithelial to mesenchymal transition Stromal targeting Pancreatic neuronal targeting microRNA 

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Copyright information

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

Authors and Affiliations

  1. 1.Division of Medical OncologyDuke Cancer Institute, Duke University Medical CenterDurhamUSA

Section editors and affiliations

  • John Neoptolemos
    • 1
  • Raul A. Urrutia
    • 2
  • James L. Abbruzzese
    • 3
  • Markus W. Büchler
    • 4
  1. 1.Division of Surgery and OncologyUniversity of LiverpoolLiverpoolUK
  2. 2.Mayo Clinic Cancer CenterMayo ClinicRochesterUSA
  3. 3.Division of Medical Oncology, Duke Cancer InstituteDuke University Medical CenterDurhamUSA
  4. 4.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany

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