Abstract
Introduction: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. Areas covered: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. Expert opinion: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the therapeutic stranding of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its actors (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.
| Original language | English |
|---|---|
| Pages (from-to) | 1623-1635 |
| Number of pages | 13 |
| Journal | Expert Opinion on Therapeutic Targets |
| Volume | 19 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2 2015 |
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Keywords
- DNA methylation
- epigenetics
- hepatocellular carcinoma
- microRNAs
- platelets
- sorafenib
- tivantinib
- VEGF
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Clinical Biochemistry
- Molecular Medicine
Cite this
Hepatocellular carcinoma treatment over sorafenib : Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel? / Gnoni, Antonio; Santini, Daniele; Scartozzi, Mario; Russo, Antonio; Licchetta, Antonella; Palmieri, Vincenzo; Lupo, Luigi; Faloppi, Luca; Palasciano, Giuseppe; Memeo, Vincenzo; Angarano, Gioacchino; Brunetti, Oronzo; Guarini, Attilio; Pisconti, Salvatore; Lorusso, Vito; Silvestris, Nicola.
In: Expert Opinion on Therapeutic Targets, Vol. 19, No. 12, 02.12.2015, p. 1623-1635.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatocellular carcinoma treatment over sorafenib
T2 - Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?
AU - Gnoni, Antonio
AU - Santini, Daniele
AU - Scartozzi, Mario
AU - Russo, Antonio
AU - Licchetta, Antonella
AU - Palmieri, Vincenzo
AU - Lupo, Luigi
AU - Faloppi, Luca
AU - Palasciano, Giuseppe
AU - Memeo, Vincenzo
AU - Angarano, Gioacchino
AU - Brunetti, Oronzo
AU - Guarini, Attilio
AU - Pisconti, Salvatore
AU - Lorusso, Vito
AU - Silvestris, Nicola
PY - 2015/12/2
Y1 - 2015/12/2
N2 - Introduction: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. Areas covered: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. Expert opinion: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the therapeutic stranding of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its actors (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.
AB - Introduction: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. Areas covered: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. Expert opinion: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the therapeutic stranding of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its actors (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.
KW - DNA methylation
KW - epigenetics
KW - hepatocellular carcinoma
KW - microRNAs
KW - platelets
KW - sorafenib
KW - tivantinib
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84952876608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952876608&partnerID=8YFLogxK
U2 - 10.1517/14728222.2015.1071354
DO - 10.1517/14728222.2015.1071354
M3 - Article
C2 - 26212068
AN - SCOPUS:84952876608
VL - 19
SP - 1623
EP - 1635
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
SN - 1472-8222
IS - 12
ER -