TY - CHAP
T1 - Signaling pathways in hepatocellular carcinoma
AU - Garcia-Lezana, Teresa
AU - Lopez-Canovas, Juan Luis
AU - Villanueva, Augusto
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Despite the recent introduction of new effective systemic agents, the survival of patients with hepatocellular carcinoma (HCC) at advanced stages remains dismal. This underscores the need for new therapies, which has spurred extensive research on the identification of the main drivers of pathway de-regulation as a source of novel therapeutic targets. Frequently altered pathways in HCC involve growth factor receptors (e.g., VEGFR, FGFR, TGFA, EGFR, IGFR) and/or its cytoplasmic intermediates (e.g., PI3K-AKT-mTOR, RAF/ERK/MAPK) as well as key pathways in cell differentiation (e.g., Wnt/β-catenin, JAK/STAT, Hippo, Hedgehog, Notch). Somatic mutations, chromosomal aberrations and epigenetic changes are common mechanisms for pathway deregulation in HCC. Aberrant pathway activation has also been explored as a biomarker to predict response to specific therapies, but currently, these strategies are not implemented when deciding systemic therapies in HCC patients. Beyond the well-established molecular cascades, there are numerous emerging signaling pathways also deregulated in HCC (e.g., tumor microenvironment, non-coding RNA, intestinal microbiota), which have opened new avenues for therapeutic exploration.
AB - Despite the recent introduction of new effective systemic agents, the survival of patients with hepatocellular carcinoma (HCC) at advanced stages remains dismal. This underscores the need for new therapies, which has spurred extensive research on the identification of the main drivers of pathway de-regulation as a source of novel therapeutic targets. Frequently altered pathways in HCC involve growth factor receptors (e.g., VEGFR, FGFR, TGFA, EGFR, IGFR) and/or its cytoplasmic intermediates (e.g., PI3K-AKT-mTOR, RAF/ERK/MAPK) as well as key pathways in cell differentiation (e.g., Wnt/β-catenin, JAK/STAT, Hippo, Hedgehog, Notch). Somatic mutations, chromosomal aberrations and epigenetic changes are common mechanisms for pathway deregulation in HCC. Aberrant pathway activation has also been explored as a biomarker to predict response to specific therapies, but currently, these strategies are not implemented when deciding systemic therapies in HCC patients. Beyond the well-established molecular cascades, there are numerous emerging signaling pathways also deregulated in HCC (e.g., tumor microenvironment, non-coding RNA, intestinal microbiota), which have opened new avenues for therapeutic exploration.
KW - Growth factors
KW - HCC
KW - Hedgehog
KW - Hippo
KW - JAK/STAT
KW - Notch
KW - Signaling pathways
KW - TGF-β
KW - Wnt/β-catenin
UR - http://www.scopus.com/inward/record.url?scp=85096876494&partnerID=8YFLogxK
U2 - 10.1016/bs.acr.2020.10.002
DO - 10.1016/bs.acr.2020.10.002
M3 - Chapter
C2 - 33579428
AN - SCOPUS:85096876494
SN - 9780128240304
T3 - Advances in Cancer Research
SP - 63
EP - 101
BT - Mechanisms and Therapy of Liver Cancer
A2 - Sarkar, Devanand
A2 - Fisher, Paul B.
PB - Academic Press Inc.
ER -