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Gastrointestinal cancer

ADAM8 provides new hope in pancreatic cancer

Nature Reviews Clinical Oncology volume 12, page 126 (2015)Cite this article

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Pancreatic Ductal Adenocarcinoma (PDAC) is the most common form of pancreatic cancer with high mortality and a 5-year survival rate <5%. The majority of PDACs (95%) are associated with mutations in the KRAS gene. Notably, a poor prognosis for patients with this disease has also been correlated with elevated expression levels of ADAM8, a metalloproteinase-disintegrin that is upregulated in PDAC cells, and could provide a new target for the treatment of PDAC as indicated by Jörg-Walter Bartsch and colleagues in their recent publication.

Synthesized in a proform, ADAM8 needs to multimerize to exert its biological function. The researchers, therefore, designed a peptidomimetic inhibitor, BK-1361, that prevents ADAM8 multimerization and sought to validate this inhibitor. “We employed biochemical methods to characterize the function of the ADAM8 inhibitor and the effect of this inhibition on tumour-cell signalling,” explains Bartsch. He continues, “we used different mouse models of PDAC, initially implanting genetically engineered human pancreatic cancer cells in the pancreas of mice and then using a genetic mouse model of PDAC that matched the human pathology.”

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References

  1. Schlomann, U. et al. ADAM8 as a drug target in pancreatic cancer. Nat. Comm. 10.1038/ncomms7175

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Authors
  1. Alessia Errico
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Errico, A. ADAM8 provides new hope in pancreatic cancer. Nat Rev Clin Oncol 12, 126 (2015). https://doi.org/10.1038/nrclinonc.2015.22

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