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Deconstructing Pancreatic Adenocarcinoma by Targeting the Conductor, MYC

Isabel A English1, Rosalie C Sears2,3,4

  • 1Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.

Cancer Discovery
|April 3, 2020
PubMed

Insights

MYC is a reversible driver of pancreatic cancer progression. Its removal causes rapid tumor regression via intrinsic and extrinsic mechanisms, supporting MYC as a therapeutic target.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Oncology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy.
  • The role of MYC in PDAC progression is not fully understood.
  • Targeting oncogenic drivers is a key therapeutic strategy.

Purpose of the Study:

  • To investigate the role of MYC as a driver in PDAC.
  • To determine the effects of MYC abrogation on established PDAC tumors.
  • To explore the mechanisms underlying MYC-driven tumor progression and regression.

Main Methods:

  • Utilized a genetically engineered mouse model of PDAC with mutant KRAS and inducible MYC.
  • Administered a drug to abrogate MYC expression in established tumors.
  • Analyzed tumor regression and associated cellular and molecular changes.

Main Results:

  • MYC acts as a critical and reversible driver of PDAC progression.
  • Abrogation of MYC led to rapid and complete tumor regression.
  • Tumor regression occurred through both cancer cell-intrinsic and cancer cell-extrinsic mechanisms.

Conclusions:

  • MYC is essential for maintaining PDAC tumor growth and progression.
  • Reversible targeting of MYC can induce significant tumor regression.
  • MYC represents a promising therapeutic target for pancreatic cancer.

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