PMID- 24985059
OWN - NLM
STAT- MEDLINE
DCOM- 20150804
LR  - 20141202
IS  - 1879-0461 (Electronic)
IS  - 1040-8428 (Linking)
VI  - 92
IP  - 2
DP  - 2014 Nov
TI  - Nras in melanoma: targeting the undruggable target.
PG  - 107-22
LID - S1040-8428(14)00084-5 [pii]
LID - 10.1016/j.critrevonc.2014.05.005 [doi]
AB  - RAS belongs to the guanosine 5'-triphosphate (GTP)-binding proteins' family, and 
      oncogenic mutations in codons 12, 13, or 61 of RAS family occur in approximately 
      one third of all human cancers with N-RAS mutations found in about 15-20% of 
      melanomas. The importance of RAS signaling as a potential target in cancer is 
      emphasized not only by the prevalence of RAS mutations, but also by the high 
      number of RAS activators and effectors identified in mammalian cells that places 
      the RAS proteins at the crossroads of several, important signaling networks. Ras 
      proteins are crucial crossroads of signaling pathways that link the activation of 
      cell surface receptors with a wide variety of cellular processes leading to the 
      control of proliferation, apoptosis and differentiation. Furthermore, oncogenic 
      ras proteins interfere with metabolism of tumor cells, microenvironment's 
      remodeling, evasion of the immune response, and finally contributes to the 
      metastatic process. After 40 years of basic, translational and clinical research, 
      much is now known about the molecular mechanisms by which these monomeric 
      guanosine triphosphatase-binding proteins promote cellular malignancy, and it is 
      clear that they regulate signaling pathways involved in the control of cell 
      proliferation, survival, and invasiveness. In this review we summarize the 
      biological role of RAS in cancer by focusing our attention on the biological 
      rational and strategies to target RAS in melanoma.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Mandala, Mario
AU  - Mandala M
AD  - Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni 
      XXIII Hospital, Bergamo, Italy. Electronic address: mariomandala@tin.it.
FAU - Merelli, Barbara
AU  - Merelli B
AD  - Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni 
      XXIII Hospital, Bergamo, Italy.
FAU - Massi, Daniela
AU  - Massi D
AD  - Division of Pathological Anatomy, Department of Surgery and Translational 
      Medicine, University of Florence, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140612
PL  - Netherlands
TA  - Crit Rev Oncol Hematol
JT  - Critical reviews in oncology/hematology
JID - 8916049
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Membrane Proteins)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (NRAS protein, human)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - GTP Phosphohydrolases/*antagonists & inhibitors/genetics
MH  - Humans
MH  - Melanoma/*drug therapy/genetics/*metabolism
MH  - Membrane Proteins/*antagonists & inhibitors/genetics
MH  - *Molecular Targeted Therapy
MH  - Mutation/genetics
MH  - Signal Transduction
OTO - NOTNLM
OT  - Melanoma
OT  - NRAS
OT  - Predictive
OT  - Prognostic
OT  - Resistance
EDAT- 2014/07/06 06:00
MHDA- 2015/08/05 06:00
CRDT- 2014/07/03 06:00
PHST- 2014/01/29 00:00 [received]
PHST- 2014/05/01 00:00 [revised]
PHST- 2014/05/09 00:00 [accepted]
PHST- 2014/07/03 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/08/05 06:00 [medline]
AID - S1040-8428(14)00084-5 [pii]
AID - 10.1016/j.critrevonc.2014.05.005 [doi]
PST - ppublish
SO  - Crit Rev Oncol Hematol. 2014 Nov;92(2):107-22. doi: 
      10.1016/j.critrevonc.2014.05.005. Epub 2014 Jun 12.