Development of a specific targeted therapy for hepatocellular carcinoma - Year two
The global burden of hepatocellular carcinoma (HCC) is increasing as it has become the second leading cause of cancer-relateddeaths and the fifth most common cancer worldwide. HCC is heterogenous, arising in the setting of various chronic liver diseasessuch as hepatitis C, non-alcoholic fatty liver disease and cirrhosis. Patients with cirrhosis who develop cancer cannot tolerate therapydue to inadequate liver function. We hypothesize that PorphyHDL, a carrier that behaves like a lipoprotein (fat transporter), willeffectively deliver a small interfering RNA targeting spalt-like transcription factor 4 (SALL4), a fetal oncoprotein expressed inaggressive HCCs. We will partner with Highland Therapeutics Inc., which has designed a novel oral drug delivery technology knownas DELEXIS® and has successfully commercialized a DELEXIS methylphenidate formulation in the US. Our partner will utilize thistechnology, which precisely controls time of release and rate of release of an active ingredient, to design a DELEXIS-PorphyHDLSALL4 formulation. This formulation will be targeted to specific regions of the gastrointestinal (GI) tract to facilitate uptake into thehepatic portal vein, with the aim of delivering drug directly to HCC tumors and avoiding side effects associated with systemiccirculation.