How does the VASH2 targeting therapy work? (Part 2)

The causes of pancreatic cancer are the activation of RAS, which is responsible for the growth signal, and the dysfunction of p53, which is responsible for apoptosis (cell death) when the growth signal becomes abnormal. Mice genetically engineered to cause such abnormalities in the pancreas (KPC mice) are used as an animal model of spontaneous pancreatic cancer. We have mice lacking the VASH2 gene, and when we crossed our mice with KPC mice, KPC mice developed pancreatic cancer in the same way even if the VASH2 gene was deleted. So VASH2 is not directly involved in the development of pancreatic cancer.

Cancer cells are pathologically classified into "well-differentiated", "moderately-differentiated", "poorly-differentiated ", or "undifferentiated" depending on how much the normal morphology is maintained, and when the degree of differentiation is low, those cancer cells are more malignant and tend to proliferate and metastasize actively. Deletion of the VASH2 gene did not alter the morphology of pancreatic cancer cells in KPC mice, but the metastasis was found to be clearly and significantly reduced. In other words, VASH2 is directly linked to metastasis regardless of the degree of differentiation of cancer cells. It turns out that the inhibition of VASH2 would control the metastasis regardless of the degree of differentiation of pancreatic cancer cells.