Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only ...Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.展开更多
慢性乙型肝炎病毒感染(chronic hepatitis B infection,CHB)诱导肝细胞的染色体超倍化(包括非整倍化和多倍化)及染色体不稳定性,是导致原发性肝细胞癌(primary hepatocytic carcinoma,HCC)发生的主要原因之一.尽管肝细胞对于正常条件下...慢性乙型肝炎病毒感染(chronic hepatitis B infection,CHB)诱导肝细胞的染色体超倍化(包括非整倍化和多倍化)及染色体不稳定性,是导致原发性肝细胞癌(primary hepatocytic carcinoma,HCC)发生的主要原因之一.尽管肝细胞对于正常条件下染色体复制的多倍体化具有调节作用,但对于CHB引起的超倍化难以调节从而致癌.研究表明,乙型肝炎病毒(hepatitis B virus,HBV)使得多条信号途径如PLK1/PRC1失调,诱导肝细胞染色体超倍化并发生恶性转化.本论文综述了HBV感染诱导肝细胞染色体超倍化导致肝癌发生的机制以及靶向染色体超倍化药物研究的最新进展.展开更多
文摘Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.
文摘慢性乙型肝炎病毒感染(chronic hepatitis B infection,CHB)诱导肝细胞的染色体超倍化(包括非整倍化和多倍化)及染色体不稳定性,是导致原发性肝细胞癌(primary hepatocytic carcinoma,HCC)发生的主要原因之一.尽管肝细胞对于正常条件下染色体复制的多倍体化具有调节作用,但对于CHB引起的超倍化难以调节从而致癌.研究表明,乙型肝炎病毒(hepatitis B virus,HBV)使得多条信号途径如PLK1/PRC1失调,诱导肝细胞染色体超倍化并发生恶性转化.本论文综述了HBV感染诱导肝细胞染色体超倍化导致肝癌发生的机制以及靶向染色体超倍化药物研究的最新进展.
