In Vivo RNAi Screening for Pancreatic Cancer Drivers: PILOTing the WDR5-MYC Axis

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Günter Schneider1, Dieter Saur1

  • 1Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 München, Germany; German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Trends in Cancer
|July 26, 2017
PubMed

Insights

Researchers developed a novel mouse model (PILOT) for pancreatic cancer research. This system identified a WDR5-Myc pathway crucial for cancer growth, offering new therapeutic targets for this deadly disease.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with poor treatment outcomes.
  • Existing therapies for PDAC show limited efficacy due to treatment resistance.
  • There is a critical need for novel strategies to identify and target PDAC drivers.

Purpose of the Study:

  • To develop a novel genetic mouse system for functional in vivo screening of PDAC.
  • To identify novel therapeutic targets and drivers of PDAC progression.
  • To investigate the role of epigenetic modifiers in PDAC.

Main Methods:

  • Development of the Patient-Based In Vivo Lethality to Optimize Treatment (PILOT) mouse system.
  • Execution of functional RNAi-based in vivo screens.
  • Forward genetic screening focused on epigenetic modifiers.

Main Results:

  • Identification of a WDR5-Myc axis regulating the DNA replication checkpoint in PDAC.
  • Demonstration of the axis's role as a potential therapeutic target.
  • Successful application of the PILOT system for uncovering PDAC drivers.

Conclusions:

  • The PILOT system is a powerful tool for PDAC research and drug discovery.
  • The WDR5-Myc axis represents a promising therapeutic target for pancreatic cancer.
  • Targeting epigenetic modifiers offers a viable strategy for PDAC treatment.

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