Development Characterization and Commercialization of a Viably Frozen Patient Inclusive Hepatocellular Carcinoma Tumor Bank

Abstract Hepatocellular carcinoma HCC is a disease of growing incidence globally including in the US by per year With the recent success of anti viral therapies the etiology of HCC in the American population is projected to shift from viral HBV HCV hepatitis to primarily fatty liver disease in the near future Currently only one effective systemic therapy has been developed for HCC the multi kinase inhibitor sorafenib The development of more selective molecularly targeted therapies has so far been unsuccessful in this disease This failure is due in part to the lack of a preclinical patient derived xenograft PDX enabling HCC tumor bank drawn from an American HCC patient population to help patient selection and model new therapies In addition modeling underlying liver disease has rarely been pursued in preclinical drug development PDX enabling tumor banks exist in Asia but tend to be from viral and alcohol driven disease as opposed to obesity which is the driver of growing incidence in the West Massachusetts General Hospital MGH has begun collecting primary patient HCC tumors from surgeries performed in Boston and will partner with Woodland Pharmaceuticals the applicant to expand these into a PDX resource better enabling new HCC therapy development Woodland will expand the tumors to up to five passages in mice and then characterize the passages for drug sensitivity both in vitro and in vivo to a panel of drugs Demonstration of stable expansion will lead to a phase application to further expand and characterize the HCC tumor bank including tracking of patient treatment and outcomes at the academic site in models with underlying liver disease in readiness for PDX service commercialization in the USA Narrative Hepatocellular carcinoma HCC is a disease of multiple etiologies viral obesity toxins whose incidence is on the rise yet has only very limited treatment options and a dismal prognosis Development of new tailored targeted therapies especially for non virally driven HCC has been held back by a lack of American e g obesity driven HCC tumor banks This proposal aims to grow and characterize such a tumor bank to enable the in vivo testing of new therapy approaches in specific subsets of HCC