A review of cutting-edge therapies for hepatocellular carcinoma (HCC): Perspectives from patents

Rationale: Hepatocellular carcinoma (HCC) is a challenging disease due to its heterogenous etiology. Several breakthroughs have occurred in treatment of HCC, associated with an enormous number of patent publications for a variety of HCC treatment modalities. As patents can provide valuable information for academic research and commercial development, this study aims to unravel the cutting-edge therapies for HCC by using patents as an indicator. The outcome from this analysis may offer meaningful insights for respective policymaking, strategic plan and research and development (R&D) prioritization. Methods: Derwent Innovation platform was employed to collect the sample data of patents related to HCC treatment technologies worldwide as of December 31, 2019. Data inclusion, screening and exclusion were according to the rules of preferred reporting items for systematic reviews and meta-analyses (PRISMA). Technologies were classified based on Barcelona Clinic Liver Cancer (BCLC) staging system and recent clinical publications. Patent citation network analysis was carried out to identify and understand HCC therapeutic technology flow. Results: A dataset of 2543 patent documents and 528 patent families was generated. 11 technological categories were classified. Numerous researches were focalized on refinements in technologies and innovations within the field of HCC therapy, and the major achievements are technology advancement on molecular target therapy, chemotherapy, locoregional therapy, combination therapy and immunotherapy with demonstrated clinical benefits. In patent citation network, Notch pathway investigation, antibody drug conjugate (ADC) technology development and drug eluting beads trans artery chemoembolization (DEB-TACE) advancement are the major technological communities involving patents with the greatest future exploratory potential. Conclusion: Numerous emerging technologies have been identified in this study, in which exploring novel therapeutic targets in molecular target therapy, more localized and visible locoregional therapy and combination of immunotherapy with target therapy or other traditional therapies are highlighted as the future trends in treating HCC.