A dual histone deacetylase and glycogen synthase kinase 3 beta inhibitor for treating pancreatic adenocarcinoma

ABSTRACT Pancreatic cancer is a disease with no effective treatmentIt s low five year survival rateestimated at betweenandranks it the fourth highest of cancer related of death in the U Sdespite being the twelfth most common type of cancerEach year in the U Sthere are nearlynew cases and more thandeaths caused by the diseaseBypancreatic cancer is expected to be the second most common cancer related cause of death in the U SResistance of pancreatic cancer to current treatment regimensboth surgery and chemotherapycontributes to the dismal prognosis of this malignancyThe current standard of care for pancreatic cancer is chemotherapynamely gemcitabineAbraxane and the Folfirinox regimensLess thanof patients respond after enduring treatmentmonths of treatment costing $The price is high given the poor outcomeDisease progression is delayed an average ofmonths and death bymonthsDuring the past decademore thanphase II III clinical trials sought out cures for pancreatic cancerand none was successfulToday s most effective regimens carry significant toxicities and offer marginal durable efficacyThusthere is a clear and unmet need for significant improvements in pancreatic cancer therapyTo this endAvenzoar has developed a novel new chemical entityAPthat interacts simultaneously with two proteins that are highly activated in pancreatic adenocarcinomaPDACGlycogen synthase kinasebetaGSKand histone deacetylaseHDACThis Phase I project will establish dosage levels of APfor animal studiesand then test the combination of APwith standard treatments in a mouse model of pancreatic adenocarcinomaPDACto determine relative efficacy as a key step to inform clinical trial design Project Narrative Pancreatic cancer is one of the deadliest forms of cancerwithof patients dying within a year and as few asof patients surviving for five yearsAPis a novel compound with low toxicity that has the potential to augment the limited efficacy of current treatment regimens by inhibiting metastasis and chemo resistance signaling pathwayswhile reversing the disorders of immune regulation caused by the cancerIts development could significantly improve prognosis and fill the critical need for effective pancreatic cancer therapy