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Protein kinase D enzymes: novel kinase targets in pancreatic cancer

Geou-Yarh Liou1, Peter Storz

  • 1a Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.

Expert Review of Gastroenterology & Hepatology
|July 16, 2015
PubMed

Insights

Pancreatic ductal adenocarcinoma (PDA) is a complex cancer. Protein kinase D enzymes are newly identified as key drivers downstream of Kras mutations, offering potential new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Pancreatic ductal adenocarcinoma (PDA) presents as advanced, desmoplastic tumors with frequent genetic alterations.
  • PDA pathogenesis is associated with activating Kras mutations and epidermal growth factor receptor (EGFR) signaling, which can further activate wild-type Kras.
  • Targeting Kras directly is challenging, necessitating the identification of downstream effectors crucial for PDA development and progression.

Discussion:

  • Protein kinase D (PKD) enzymes are upregulated in PDA and implicated in its development and progression.
  • PKD acts downstream of both mutant Kras and growth factor signaling pathways.
  • This positions PKD as a promising novel therapeutic target for PDA.

Key Insights:

  • Kras mutations are a hallmark of PDA, but direct targeting remains difficult.
  • Protein kinase D enzymes are increasingly expressed in PDA.
  • PKD functions downstream of oncogenic Kras and growth factor pathways in PDA.

Outlook:

  • Further investigation into PKD's role in PDA could reveal new therapeutic strategies.
  • Targeting PKD may offer a viable approach to inhibit PDA progression driven by Kras.
  • Understanding the downstream signaling of Kras in PDA is critical for developing effective treatments.
Keywords:
acinar-to-ductal metaplasiaisoformspancreatic cancerprotein kinase D

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