Cancer cell dormancy in novel mouse models for reversible pancreatic cancer: A lingering challenge in the development of targeted therapies

Wan Chi Lin, Nirakar Rajbhandari, Kay Uwe Wagner

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Significant advances have been made in the identification of key molecular pathways that play pivotal roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). Among the common genetic and epigenetic changes, oncogenic mutations in Kras and upregulation of the c-Myc oncogene are frequent events in PDAC. Using genetically defined in vivo models, several studies have recently demonstrated that expression of mutant Kras and c-Myc is equally important for the initiation and maintenance of pancreatic cancer. The targeted downregulation of a single oncogene resulted in cancer cell death at primary and metastatic sites. These findings are very encouraging and provide a strong rationale for the development of targeted therapies against these oncogenic drivers. Despite what seemed to be a complete response to the ablation of the oncogene, a few dormant cancer cells remained present, and it was demonstrated that they are a cellular reservoir for a swift relapse of pancreatic cancer following oncogene reactivation. This review summarizes the basic principles of cancer dormancy and the applicability of the novel genetic models for reversible metastatic PDAC to elucidate the role of cancer stem cells as well as biologic and molecular mechanisms that mediate the survival of dormant tumor cells.

Original languageEnglish (US)
Pages (from-to)2138-2143
Number of pages6
JournalCancer Research
Volume74
Issue number8
DOIs
StatePublished - Apr 15 2014

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Pancreatic Neoplasms
Oncogenes
Adenocarcinoma
Neoplasms
myc Genes
Neoplastic Stem Cells
Genetic Models
Therapeutics
Epigenomics
Cell Death
Up-Regulation
Down-Regulation
Maintenance
Recurrence
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cancer cell dormancy in novel mouse models for reversible pancreatic cancer : A lingering challenge in the development of targeted therapies. / Lin, Wan Chi; Rajbhandari, Nirakar; Wagner, Kay Uwe.

In: Cancer Research, Vol. 74, No. 8, 15.04.2014, p. 2138-2143.

Research output: Contribution to journalArticle

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