Hepatocellular carcinoma treatment over sorafenib: Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?

Antonio Gnoni, Daniele Santini, Mario Scartozzi, Antonio Russo, Antonella Licchetta, Vincenzo Palmieri, Luigi Lupo, Luca Faloppi, Giuseppe Palasciano, Vincenzo Memeo, Gioacchino Angarano, Oronzo Brunetti, Attilio Guarini, Salvatore Pisconti, Vito Lorusso, Nicola Silvestris

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1623-1635
Number of pages13
JournalExpert Opinion on Therapeutic Targets
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 2 2015

Fingerprint

MicroRNAs
Epigenomics
Tumors
Hepatocellular Carcinoma
Histone Deacetylase Inhibitors
Immune system
Genetic Epigenesis
Biological Factors
Biomarkers
Platelets
Tumor Microenvironment
Tunnels
DNA Methylation
Therapeutics
Cytokines
Genetic Phenomena
sorafenib
Expert Testimony
Immune System
Carcinogenesis

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 journalArticle

Gnoni, A, Santini, D, Scartozzi, M, Russo, A, Licchetta, A, Palmieri, V, Lupo, L, Faloppi, L, Palasciano, G, Memeo, V, Angarano, G, Brunetti, O, Guarini, A, Pisconti, S, Lorusso, V & Silvestris, N 2015, 'Hepatocellular carcinoma treatment over sorafenib: Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?', Expert Opinion on Therapeutic Targets, vol. 19, no. 12, pp. 1623-1635. https://doi.org/10.1517/14728222.2015.1071354
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. / Hepatocellular carcinoma treatment over sorafenib : Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?. In: Expert Opinion on Therapeutic Targets. 2015 ; Vol. 19, No. 12. pp. 1623-1635.
@article{053330ad90c147749dabd39cbb85a560,
title = "Hepatocellular carcinoma treatment over sorafenib: Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel?",
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.",
keywords = "DNA methylation, epigenetics, hepatocellular carcinoma, microRNAs, platelets, sorafenib, tivantinib, VEGF",
author = "Antonio Gnoni and Daniele Santini and Mario Scartozzi and Antonio Russo and Antonella Licchetta and Vincenzo Palmieri and Luigi Lupo and Luca Faloppi and Giuseppe Palasciano and Vincenzo Memeo and Gioacchino Angarano and Oronzo Brunetti and Attilio Guarini and Salvatore Pisconti and Vito Lorusso and Nicola Silvestris",
year = "2015",
month = "12",
day = "2",
doi = "10.1517/14728222.2015.1071354",
language = "English",
volume = "19",
pages = "1623--1635",
journal = "Expert Opinion on Therapeutic Targets",
issn = "1472-8222",
publisher = "Informa Healthcare",
number = "12",

}

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 -