Methods for identifying and treating pancreatic cancer with ROCK1 therapeutic target


Researchers at TGen have developed a method for identifying and treating pancreatic cancer.  Through the identification of the ROCK1 gene as a therapeutic target, pancreatic cancer can be detected and tumor cell proliferation and migration can be inhibited using the inventive methods.


Pancreatic cancer is a prevalent cause of tumor related deaths in the industrialized world, with surgery providing a viable treatment option for only a minority of patients.  Survival after diagnosis of pancreatic cancer is particularly challenging because traditional medicine has provided no modality for early detection and reports of effective treatment for advanced pancreatic cancer, either local or metastatic disease, have been few.


TGen has demonstrated ROCK1 to be a valuable therapeutic target for the inhibition of the stromal contribution to tumor growth in pancreatic ductal adenocarcinoma (PDAC).  ROCK1 was found to be

overexpressed in human pancreatic tumor cells and amplified in a subset PDAC patent samples.  To evaluate potential treatment of overexpression or amplification of ROCK1, TGen screened ROCK1 inhibitors for efficacy in pancreatic cancer cell lines.  The small molecule ROCK1 inhibitors screened by TGen included fasudil (5-(1,4-diazepan-1-ylsulfonyl)isoquinoline), derivatives of fasudil (e.g., fasudil hydrochloride (INN) (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride)), and Y-27632 (4-(1-aminoethyl)-N-pyridin-4-yl-cyclohexane-1-carboxamide).


Fasudil was shown to not only selectively inhibit human fibroblast proliferation, but inhibit collagen synthesis in primary human fibroblast cells as well.  Histochemical analyses demonstrate significantly reduced collagen deposition in fasudil-treated mouse tumors.  Additionally, the identified ROCK1 inhibitors also showed inhibition of aSMA and collagen 1 expressing myofibroblasts, a reduction in collagen synthesis, and a reduction in the stromal contribution to tumor growth.  The TGen-developed technology leveraging the ROCK1 gene as a therapeutic target has further application in screening additional agents for inhibition of ROCK1 activity and effective treatment of pancreatic cancer.


Link to US Issued Patent 8,703,736

Patent Information:
For Information, Contact:
Katie Bray
Intellectual Property Counsel
The Translational Genomics Research Institute
Haiyong Han
Clifford Whatcott
Daniel Von Hoff
Michael Barrett