Molecular signatures in hepatocellular carcinoma: A step toward rationally designed cancer therapy

Abstract

Molecular characterization of hepatocellular carcinoma (HCC) has greatly improved our understanding of disease pathogenesis. Mutational analysis, RNA and microRNA expression profiling, and epigenetic characterization have revealed common aberrations in oncogenes and tumor suppressors that correlate with disease biology and serve as a guide for the rational design of targeted therapies. These approaches have also led to the discovery of novel targets, including mutations in isocitrate dehydrogenase and chromatin remodeling enzymes. With the advent of immunotherapy, RNA expression profiling of the tumor microenvironment has identified a subset of HCC with high lymphocyte infiltration that may benefit from checkpoint inhibitor therapy. Molecular signatures thus capture the biology of a tumor, providing a supplement to current staging schema, which are based on tumor size and number, for more accurate prognostication of recurrence risk and survival. Molecular signatures may also be used to guide interventional therapy by defining those most suitable for transplantation or locoregional therapy rather than surgical resection. Finally, a multiomics approach involves the aggregation and analysis of multiple signatures for a more comprehensive characterization of pathogenic mechanisms. This broader approach attempts to address issues with signaling pathway cross-talk and redundancy, which have greatly limited the potential value of targeted therapies to date. Cancer 2018. © 2018 American Cancer Society.

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

“…Numerous studies have described so-called "miRNA signatures" associated with specific biological functions, including cancer development and progression [13,85,[98][99][100][110][111][112]. Since one miRNA can regulate up to hundreds of different target genes in a cell [69,113,114], the administration of single miRNAs as therapeutic targets raises the problem of a potentially widespread functional heterogeneity of one miRNA in different tumors types and potential adverse side effects to normal tissue [115,116].…”

Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma

“…The expression of several microRNAs (miRNAs) also is reported to be dysregulated in many types of cancer, including NASH-associated HCC [52] . The miRNAs are small noncoding RNAs that down-regulate gene expression by interfering with transcription and/or translation.…”

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

“…With increased knowledge of the molecular-based analyses for HCC [33,34], various basic studies are ongoing to develop novel gene therapy for HCC. These studies include epigenetic changes [35], integration in the genome [36], protein expression [37], endothelial growth factor receptor (EGFR) signaling pathway [38], EGFR/ Hypoxia Inducible Factor-1α/vascular EGF (VEGF) pathways under hypoxic conditions [39][40][41], target gene discovery through copy number alteration [42], and genomic profiling of rare liver cancer [43].…”