Study Identifies Mechanisms of Metastasis in Subtype of Pancreatic Cancer

Aislinn Antrim, Associate Editor

The basal subtype of ductal adenocarcinoma can be identified by the presence of the DeltaNp63 protein.

New research led by the Institute of Cancer Research and Comprehensive Cancer Center in Vienna has identified specific mechanisms that lead to aggressive metastasis in the basal subtype of ductal adenocarcinoma (PDAC), a type of pancreatic cancer.1

Pancreatic cancer tends to be aggressive, with a 10% 5-year survival rate, according to the American Society of Clinical Oncology. Part of this survival rate is attributable to the lack of validated, specific screening tests to identify early-stage pancreatic cancer in patients without symptoms.2 Additionally, approximately 11% of patients are diagnosed at an early stage when surgical removal of the tumor is possible.2

PDAC is known to be the most prevalent form of pancreatic cancer. It is typically divided into a classical subtype and a basal subtype, the latter of which is highly aggressive and tends to metastasize early. One of the distinguishing features is that the classical subtype exhibits the GATA-binding factor 6 (GATA6) protein, whereas the DeltaNp63 protein can be detected in the basal subtype.1

According to the press release, the switch-over of the cancer cells from the classical to the basal occurs in 2 phases. First, the GATA6 protein is lost, although the investigators noted that this is not enough for the expression of DeltaNp63. Only after the loss of both the hepatic nuclear factor 1 alpha and hepatocyte nuclear factor 4 alpha proteins does DeltaNp63 emerge, and the tumor becomes more aggressive.1

“This suggests that reinstating the classical subtype could serve to reduce metastasis,” said the study’s lead author Paola Martinelli, PhD, the research group leader at the Institute of Cancer Research and member of the Comprehensive Cancer Center of the Medical University of Vienna and Vienna General Hospital, in the press release. “Moreover, the tumor would once again be easier for the immune system to detect, since GATA6 not only hinders the ability of tumors to adapt to their surroundings but also blocks the mechanisms that hide tumors from the immune system.”1

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