Pancreatic cancer

Jorg Kleeff, Murray Korc, Minoti Apte, Carlo La Vecchia, Colin D. Johnson, Andrew V. Biankin, Rachel E. Neale, Margaret Tempero, David A. Tuveson, Ralph H. Hruban, John P. Neoptolemos

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4-none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.

Original languageEnglish (US)
Article number16022
JournalNature Reviews Disease Primers
Volume2
DOIs
StatePublished - Apr 21 2016

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Pancreatic Neoplasms
p16 Genes
Neoplasms
Neoadjuvant Therapy
Tumor Microenvironment
Survival
Drug Combinations
Stromal Cells
Epigenomics
Early Diagnosis
Quality of Life
Recurrence
Mutation
Mortality
Therapeutics
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., ... Neoptolemos, J. P. (2016). Pancreatic cancer. Nature Reviews Disease Primers, 2, [16022]. https://doi.org/10.1038/nrdp.2016.22

Pancreatic cancer. / Kleeff, Jorg; Korc, Murray; Apte, Minoti; La Vecchia, Carlo; Johnson, Colin D.; Biankin, Andrew V.; Neale, Rachel E.; Tempero, Margaret; Tuveson, David A.; Hruban, Ralph H.; Neoptolemos, John P.

In: Nature Reviews Disease Primers, Vol. 2, 16022, 21.04.2016.

Research output: Contribution to journalArticle

Kleeff, J, Korc, M, Apte, M, La Vecchia, C, Johnson, CD, Biankin, AV, Neale, RE, Tempero, M, Tuveson, DA, Hruban, RH & Neoptolemos, JP 2016, 'Pancreatic cancer', Nature Reviews Disease Primers, vol. 2, 16022. https://doi.org/10.1038/nrdp.2016.22
Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV et al. Pancreatic cancer. Nature Reviews Disease Primers. 2016 Apr 21;2. 16022. https://doi.org/10.1038/nrdp.2016.22
Kleeff, Jorg ; Korc, Murray ; Apte, Minoti ; La Vecchia, Carlo ; Johnson, Colin D. ; Biankin, Andrew V. ; Neale, Rachel E. ; Tempero, Margaret ; Tuveson, David A. ; Hruban, Ralph H. ; Neoptolemos, John P. / Pancreatic cancer. In: Nature Reviews Disease Primers. 2016 ; Vol. 2.
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