The Changing Landscape of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) represents one of the leading causes of cancer death and has proved to be highly refractory to treatment. Extensive analysis of the disease has demonstrated that it arises predominantly in response to high-risk etiological challenges, most notably hepatitis virus. However, with evolving vaccination and the obesity epidemic, progressively more cases are associated with underlying metabolic dysfunction. Pathologically diverse forms of HCC are observed, and recent sequencing analysis has defined common events that target well-known cancer pathways including β-catenin/Axin, TP53, and RB/CDKN2A, as well as frequent aberrations in chromatin remodeling factors. However, there are a myriad of low frequency genetic events that make each HCC case unique. Gene expression profiling approaches have successfully been deployed for prognostic assessment of hepatocellular carcinoma and to detect the earliest stages of disease. Despite more extensive research, systemic treatment for HCC is exceedingly limited, with only a handful of drugs providing benefit. Ongoing clinical trials are attempting to exploit specific biological dependencies of HCC to improve the dismal prognosis. Overall, the future of HCC treatment will rely on an understanding of the interplay between etiological factors, molecular features of disease, and rational therapeutic intervention.

A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patients

“…While these oncogenic pathways are often concordantly activated in molecular subtypes of human HCCs [8,9], the mechanistic basis of the signaling connections is largely unknown. Delineation of the signaling hubs that contribute to hepatocarcinogenesis may greatly advance therapeutic development [3,10].…”

Diagnostic and prognostic significance of secretory clusterin expression in patients with hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer and the second leading cause of cancer deaths in the world, accounting for 80-90 % patients attributed to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in company with aflatoxin B1 or alcohol [1,2]. As is known, the early manifestation of HCC is nearly asymptomatic, and the existing serum α-fetoprotein (AFP) may not be satisfactory due to approximately 40 % of negative patients.…”

Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma

“…[1][2][3] Multiple risk factors have been linked to the development of HCC, with chronic viral hepatitis (B and C) infection, alcohol abuse, non-alcoholic steatohepatitis (NASH), presence of diabetes and/or metabolic syndrome, and exposure to aflatoxins being the most frequent; nonetheless, HCC can also occur in people without any known risk factor. [4][5][6] The clear majority of HCC patients are diagnosed with an advanced disease, often precluding potentially effective therapies such as liver transplantation or curative partial liver resection. Targeted therapies against HCC are very limited.…”