PMID- 27109020
OWN - NLM
STAT- MEDLINE
DCOM- 20170531
LR  - 20191027
IS  - 1875-5992 (Electronic)
IS  - 1871-5206 (Linking)
VI  - 17
IP  - 2
DP  - 2017
TI  - Epidrugs in the Immunotherapy of Cutaneous and Uveal Melanoma.
PG  - 190-205
AB  - Epigenetic modifications can affect numerous mechanisms used by neoplastic cells 
      to evade immune control. In melanoma epigenetic defects, caused by dysregulations 
      in the expression of genome writers, erasers, or readers, play a significant role 
      in the reduced expression of molecules required for efficient immune recognition 
      as well as antigen presentation and processing. Alterations in gene expression 
      were identified in tumor-associated antigens (TAAs), human leukocyte antigen 
      (HLA) complex, co-stimulatory/accessory molecules, antigen processing machinery 
      (APM), and NKG2D ligands that have shown to be silenced or down-regulated in 
      melanoma. In agreement with the inherent reversibility of epigenetic silencing, 
      epigenetic drugs such as inhibitors of DNA methyltransferases (DNMTs), histone 
      deacetylases (HDACs), histone methyltransferase enhancer of Zeste homolog 2 
      (EZH2), and modifiers of microRNA (miRNA) dysregulation or antagomirs can restore 
      the expression of these molecules, favouring the recognition of cancer cells by 
      immune responses, reducing the resistance to Natural Killer (NK) and cytotoxic T 
      cells (CTL), and enhancing the functions of antigen presenting cells. Moreover, 
      inhibitors of reader proteins seem to preferentially affect the NF-kB-induced 
      activation of pro-inflammatory cytokine genes. At present an increasing interest 
      is shown toward new combined therapeutic approaches employing epidrugs or new 
      molecular inhibitors and in vivo immunotherapies, such as vaccines and adoptive 
      T-cell transfer (ACT). This review summarizes the current understanding of the 
      role of epidrugs in the modulation of molecules involved in the melanoma immune 
      response and focuses on their future clinical use in new therapeutic combinations 
      for melanoma treatment.
FAU - Venza, Mario
AU  - Venza M
FAU - Visalli, Maria
AU  - Visalli M
FAU - Catalano, Teresa
AU  - Catalano T
FAU - Beninati, Concetta
AU  - Beninati C
FAU - Teti, Diana
AU  - Teti D
FAU - Venza, Isabella
AU  - Venza I
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy Department of Clinical and Experimental Medicine - Azienda Policlinico 
      Universitario G. Martino - Via Consolare Valeria, 1 - 98125 - Messina -. Italy.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Anticancer Agents Med Chem
JT  - Anti-cancer agents in medicinal chemistry
JID - 101265649
RN  - 0 (Antineoplastic Agents)
RN  - Uveal melanoma
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Epigenesis, Genetic/*drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Immunity/drug effects
MH  - Immunotherapy/*methods
MH  - Melanoma/*genetics/immunology/pathology/*therapy
MH  - Uvea/*drug effects/immunology/metabolism/pathology
MH  - Uveal Neoplasms/*genetics/immunology/pathology/*therapy
EDAT- 2016/04/26 06:00
MHDA- 2017/06/01 06:00
CRDT- 2016/04/26 06:00
PHST- 2015/09/14 00:00 [received]
PHST- 2016/04/04 00:00 [revised]
PHST- 2016/04/22 00:00 [accepted]
PHST- 2016/04/26 06:00 [pubmed]
PHST- 2017/06/01 06:00 [medline]
PHST- 2016/04/26 06:00 [entrez]
AID - ACAMC-EPUB-75151 [pii]
AID - 10.2174/1871520616666160425110401 [doi]
PST - ppublish
SO  - Anticancer Agents Med Chem. 2017;17(2):190-205. doi: 
      10.2174/1871520616666160425110401.