Targeted therapy for hepatocellular carcinoma: Challenges and opportunities. (28th September 2019)

• Record Type: Journal Article
• Authors: Chen, Shuzhen; Cao, Qiqi; Wen, Wen; Wang, Hongyang
• Is Part Of: Cancer letters. Volume 460(2019)
• Page Start: 1
• Page End: 9
• Publication Date: 2019-09-28
• Subjects: Hepatocellular carcinoma (HCC) -- Multi-kinase inhibitors (MKIs) -- Immunotherapy -- Drug resistance; HCC hepatocellular carcinoma -- MKI multikinase inhibitor -- FDA Food and Drug Administration -- ORR objective response rate -- OS overall survival -- EGF epidermal growth factor -- LPC liver progenitor cells -- TICs tumor-initiating stem-like cells -- EGFR epidermal growth factor receptor -- VEGF vascular endothelial growth factor -- VEGFR vascular endothelial growth factor receptor -- PDGF platelet-derived growth factor -- PDGFR platelet-derived growth factor receptor -- FGF fibroblast growth factor -- FGFR fibroblast growth factor receptor -- SCF stem cell factor -- c-KIT also known as CD117 -- GFRα growth factor alfa -- HGF hepatocyte growth factor -- JAK janus kinase -- NF-κB nuclear factor kappa-B -- PI3K phosphatidylinositol 3-kinase -- AKT protein kinase B -- PTEN phosphatase and tensin homolog -- mTOR mammalian target of rapamycin -- TANs Tumor-associated neutrophils -- TICs tumor initiating cells -- LPCs liver progenitor cells -- GPC3 glypican-3 -- PD-1 programmed cell death 1 -- CAR-T chimeric antigen receptor-modified T cells -- TMB tumor mutational burden -- CXCR4 cell-derived 1 alpha receptor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.114428
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, which ranks as the sixth of cancer-related death. Despite the emergence of targeted therapy, advanced-stage HCC remains largely incurable due to low response rate and therapeutic resistance. In this review, we mainly focused on the current progression of multi-kinase inhibitors and immunotherapies in the treatment of HCC. We highlight the mechanism underlying the ineffectiveness of these targeted therapies, including oncogenic alterations in driver genes and downstream pathways, high heterogeneity of HCC, and the mutual interaction of tumor microenvironment that promotes therapeutic resistance. We also discussed how these previous studies suggested for future therapeutic strategies. Besides, the complexity of HCC heterogeneity and cancer revolution need to be recognized in personalized therapy. Establishment of a drug screening system and identification of biomarkers of response is also in urgent need to overcome drug resistance. Meanwhile, a combination of targeted therapies could also be explored as a promising strategy in the future. Highlights: Despite the emergence of targeted therapy, advanced-stage HCC remains largely incurable due to therapeutic resistance. Multiple factors contribute to drug resistance of HCC patients against MKIs. Further studies are expected to identify biomarkers for response and promote efficacy of immunotherapy. Insight into heterogeneity of HCC and combined therapy could be the next step forward the future of precision medicine.