TY - JOUR
T1 - The changing landscape of hepatocellular carcinoma
T2 - Etiology, genetics, and therapy
AU - Knudsen, Erik S.
AU - Gopal, Purva
AU - Singal, Amit G.
N1 - Funding Information:
Supported by grants from NIH (E.S.K.) and the Melanoma Research Association (E.S.K.) and by contract funding from Pfizer (E.S.K.).
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2013.10.028
DO - 10.1016/j.ajpath.2013.10.028
M3 - Review article
C2 - 24388934
AN - SCOPUS:84894166118
SN - 0002-9440
VL - 184
SP - 574
EP - 583
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -