Molecular Targeted Therapy for Hepatocellular Carcinoma: Present Status and Future Directions

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most lethal neoplasm, causing an estimated 700000 deaths annually. Currently HCC has only one systemic molecular targeted therapy, the multi-kinase inhibitor, sorafenib. The standard-of-care for advanced liver cancer is limited because sorafenib can expand the median life expectancy of patients for only 1 year. Thus there is an urgent need to develop a novel molecular targeted therapy to improve therapeutic outcomes for HCC. HCCs are phenotypically and genetically heterogeneous tumors driven by diverse molecular mechanisms. However, HCCs exhibit certain common traits selected through genetic and epigenetic alterations. The identification of common molecular alterations may provide an opportunity to develop more effective anticancer treatment through targeted therapy. Recent studies in liver cancer biology have revealed a limited number of molecular targets responsible for initiating and maintaining dysregulated cell proliferation, including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), c-mesenchymal-epithelial transition factor-1 (c-Met), mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). New treatments involving inhibitors targeting several of these critical pathways are in development. This review describes the current understanding of target pathways, ongoing clinical trials using HCC-targeted agents, and future directions in the treatment of HCC.

LncRNA CASC2 inhibited the viability and induced the apoptosis of hepatocellular carcinoma cells through regulating miR‐24‐3p

“…The hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with the highest morbidity. 1 Exploring the specific mechanism of hepatocarcinogenesis and its early metastasis is of great value for early diagnosis and improving prognosis of HCC. Previous studies on the pathogenesis and development of HCC mostly focus on the traditional protein coding genes, which mainly involve the regulation of genetics, epigenetics, and related signaling pathways.…”

NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation

“…However, not all individuals exposed to these factors possess the same risk of developing HCC. It is a multifactorial disease, with a wide range of genetic and epigenetic alterations identified as contributory to the deregulation of key oncogenes and tumor-suppressor genes; however, genetic events in hepatic carcinogenesis are poorly understood (7). Previous studies undertaken by our group uncovered potential molecular targets for HCC treatment, by comparing the gene expression patterns of HCC with those of normal liver tissues using a cDNA expression microarray containing 1361 unique genes (8).…”

Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer

“…This has been attributed to the down regulation of the Ras-Raf and PI3K-Akt pathways [68]. Other targets in HCC include: glypican-3 (GC33), c-Met (onartuzumab), epidermal growth factor receptor (cetuximab), insulin-like growth factor-1 receptor (cixutumumab), insulin-like growth factor I and II (MEDI-573), platelet-derived growth factor receptor A (MEDI-575), activin receptor-like kinase 1 (PF-03446962), endoglin (TRC105), and TROP-2 (sacituzumab) [69,70,71,72,73,74,75]. Additional targets like EpCAM and CD133 are being evaluated in preclinical studies as potential markers for HCC [45,76,77,78].…”