PMID- 31766556
OWN - NLM
STAT- MEDLINE
DCOM- 20200406
LR  - 20200623
IS  - 1648-9144 (Electronic)
IS  - 1010-660X (Print)
IS  - 1010-660X (Linking)
VI  - 55
IP  - 12
DP  - 2019 Nov 21
TI  - Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer 
      Therapies.
LID - 10.3390/medicina55120754 [doi]
LID - 754
AB  - The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor 
      knowledge of its biology. For several years, sorafenib, a tyrosine kinase 
      inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for 
      advanced HCC patients. Its activity is the inhibition of the 
      retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated 
      Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated 
      kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. 
      However, the efficacy of sorafenib is limited by the development of drug 
      resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a 
      critical and central role in HCC escape from TKIs activity. Advanced HCC patients 
      with a BRAF mutation display a multifocal and/or more aggressive behavior with 
      resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied 
      in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF 
      could be another mechanism of cancer proliferation and TKI escape in HCC and the 
      inhibition could become a possible strategy treatment for HCC. Moreover, recent 
      preclinical studies and clinical trials evidence that combined treatments, 
      involving alternative pathways, have an important role of therapy for HCC and 
      they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein 
      S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of 
      rapamycin (mTOR). These initial data must be confirmed in clinical studies, which 
      are currently ongoing. Translational research discoveries could create new 
      strategies of targeted therapy combinations, including BRAF pathway, and they 
      could eventually bring light in new treatment of HCC.
FAU - Gnoni, Antonio
AU  - Gnoni A
AD  - Medical Oncology Unit, "S. Cuore di Gesu" Hospital, 73014 Gallipoli, Italy.
FAU - Licchetta, Antonella
AU  - Licchetta A
AD  - Medical Oncology Unit, "S. Cuore di Gesu" Hospital, 73014 Gallipoli, Italy.
FAU - Memeo, Riccardo
AU  - Memeo R
AD  - Department of Surgery and Liver Transplantation, Policlinico di Bari, 70124 Bari, 
      Italy.
FAU - Argentiero, Antonella
AU  - Argentiero A
AD  - Medical Oncology Unit, National Cancer Research Centre, IRCCS Istituto Tumori 
      "Giovanni Paolo II", 70124 Bari, Italy.
FAU - Solimando, Antonio G
AU  - Solimando AG
AD  - Department of Biomedical Sciences and Human Oncology, Section of Internal 
      Medicine "G. Baccelli", University of Bari Medical School, 70124 Bari, Italy.
FAU - Longo, Vito
AU  - Longo V
AD  - Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Viale 
      Orazio Flacco, 65, 70124 Bari, Italy.
FAU - Delcuratolo, Sabina
AU  - Delcuratolo S
AD  - Scientific direction, National Cancer Research Centre, IRCCS Istituto Tumori 
      "Giovanni Paolo II", 70124 Bari, Italy.
FAU - Brunetti, Oronzo
AU  - Brunetti O
AD  - Medical Oncology Unit, National Cancer Research Centre, IRCCS Istituto Tumori 
      "Giovanni Paolo II", 70124 Bari, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191121
PL  - Switzerland
TA  - Medicina (Kaunas)
JT  - Medicina (Kaunas, Lithuania)
JID - 9425208
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Hepatocellular/*drug therapy
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
MH  - Humans
MH  - Liver Neoplasms/*drug therapy
MH  - Molecular Targeted Therapy/*methods
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Proto-Oncogene Proteins B-raf/*antagonists & inhibitors
PMC - PMC6956203
OTO - NOTNLM
OT  - BRAF
OT  - MAPK pathway
OT  - MEK
OT  - Sorafenib
OT  - TKI
OT  - hepatocellular carcinoma
OT  - liver microenvironment
COIS- The authors declare the absence of conflict of interests.
EDAT- 2019/11/27 06:00
MHDA- 2020/04/09 06:00
PMCR- 2019/11/21
CRDT- 2019/11/27 06:00
PHST- 2019/09/15 00:00 [received]
PHST- 2019/11/11 00:00 [revised]
PHST- 2019/11/15 00:00 [accepted]
PHST- 2019/11/27 06:00 [entrez]
PHST- 2019/11/27 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/11/21 00:00 [pmc-release]
AID - medicina55120754 [pii]
AID - medicina-55-00754 [pii]
AID - 10.3390/medicina55120754 [doi]
PST - epublish
SO  - Medicina (Kaunas). 2019 Nov 21;55(12):754. doi: 10.3390/medicina55120754.