CDK4/6 and PDGFRA Signaling as Therapeutic Targets in Diffuse Intrinsic Pontine Glioma

Christine Hoeman1, Chen Shen1, Oren J Becher1,2

  • 1Department of Pediatrics, Northwestern University, Chicago, IL, United States.

Frontiers in Oncology
|June 16, 2018
PubMed

Insights

Genetic engineered mouse models offer new insights into diffuse intrinsic pontine gliomas (DIPGs), an incurable childhood brain tumor. This approach aids in understanding DIPG development and evaluating new treatments.

Area of Science:

  • Pediatric Oncology
  • Neuro-oncology
  • Cancer Biology

Background:

  • Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors with limited treatment options.
  • Standard care, focal radiation, offers only temporary palliation, and clinical trials have yielded few survival-extending therapies.

Purpose of the Study:

  • To explore the utility of genetic engineered mouse modeling for dissecting DIPG pathophysiology.
  • To investigate novel genetic alterations, cell of origin, and regional influences in gliomagenesis.
  • To evaluate novel therapeutic strategies in a relevant preclinical model.

Main Methods:

  • Utilized retroviral gene delivery systems to create autochthonous murine DIPG models.
  • Employed genetic engineering to induce tumor formation in specific mouse models.

Main Results:

  • Demonstrated the feasibility of generating genetically engineered mouse models for DIPG research.
  • Established a platform for interrogating genetic drivers and cell origins of DIPG.
  • Enabled the evaluation of therapeutic interventions in an immunocompetent setting.

Conclusions:

  • Genetic engineered mouse models are crucial tools for understanding DIPG pathogenesis.
  • This approach facilitates the identification of therapeutic targets and the preclinical testing of novel treatments for DIPG.
  • Further research using these models holds promise for improving outcomes in pediatric brain tumors.

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