Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most important cause of cancer death. Because of its highly heterogeneous nature, the current approach to identifying druggable targets have not delivered efficacious therapies in HCC and is a main reason for the high case fatality. Even when surgical resection is potentially curative in early disease, tumor recurrence remains high and long term survival poor because of the absence of useful adjuvant therapy. To address these unmet needs, the investigators bring together internationally recognized scientists from genomics and immunology and established clinician investigators in a synergistic team. This TCR capitalizes on recent collaborative advances made by the PIs in the consortium. The investigators have shown through multi-region sampling of freshly resected HCC and phylogenetic analysis, that significant intra-tumoral heterogeneity exists and have identified the specific positions of known clonal drivers. Simultaneously the investigators have analyzed the immune landscape of the tumor microenvironment with deep immune-phenotyping and found unique inter-patient immune landscapes predictive of clinical trajectory. This TCR is a prospective study that samples resected HCC from multi-ethnic sites within the established Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group, which has enrolled approximately 1000 patients through 6 multi-center trials in 35 centers in the region. Clinical trajectories are tracked and genomic and immunological studies are repeated when tumors recu r, to confirm clonally dominant driver mutations and immunological processes that are targetable. Concurrently, representative pre-clinical models will be developed from the tissues sampled. The investigators aim to combine these approaches to overcome the challenges posed by genomic heterogeneity and to guide the development of therapeutics and precision medicine in HCC.