PMID- 28073102
OWN - NLM
STAT- MEDLINE
DCOM- 20170210
LR  - 20181202
IS  - 1532-1967 (Electronic)
IS  - 0305-7372 (Linking)
VI  - 53
DP  - 2017 Feb
TI  - Cancer resistance to therapies against the EGFR-RAS-RAF pathway: The role of MEK.
PG  - 61-69
LID - S0305-7372(16)30142-6 [pii]
LID - 10.1016/j.ctrv.2016.12.001 [doi]
AB  - The mitogen-activated protein kinases (MAPKs) mediate intracellular signals 
      activated by a wide variety of extracellular stimuli. The activation of the 
      RAS-RAF-MEK-MAPK cascade culminates in the regulation of gene transcription 
      promoting cancer cell proliferation, survival, migration and angiogenesis. MEK 
      (mitogen-activated protein kinase kinase-MAPKK) 1/2 is a transducer of the growth 
      factor receptor-RAS-RAF-MAPK signalling cascade and plays a relevant role in 
      development and progression of human cancers, such as colorectal cancer (CRC), 
      non small cell lung cancer (NSCLC). Direct inhibition of MEK is a promising 
      strategy and several inhibitors are currently under evaluation in clinical trials 
      showing initial clinical activity in different tumours. MEK activation, by 
      different genetic mechanisms, has been described for both intrinsic and acquired 
      resistance to drugs targeting the EGFR (Epidermal Growth Factor Receptor)-RAS-RAF 
      pathway in CRC, NSCLC. Combination therapies with chemotherapy and/or with 
      molecular targeted agents are warranted and biomarkers studies are needed to 
      identify those tumours dependent on MEK signalling.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Martinelli, Erika
AU  - Martinelli E
AD  - Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. 
      Magrassi e A. Lanzara", Universita degli Studi della Campania Luigi Vanvitelli, 
      Via S. Pansini 5, 80131 Napoli, Italy. Electronic address: 
      erika.martinelli@unina2.it.
FAU - Morgillo, Floriana
AU  - Morgillo F
AD  - Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. 
      Magrassi e A. Lanzara", Universita degli Studi della Campania Luigi Vanvitelli, 
      Via S. Pansini 5, 80131 Napoli, Italy.
FAU - Troiani, Teresa
AU  - Troiani T
AD  - Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. 
      Magrassi e A. Lanzara", Universita degli Studi della Campania Luigi Vanvitelli, 
      Via S. Pansini 5, 80131 Napoli, Italy.
FAU - Ciardiello, Fortunato
AU  - Ciardiello F
AD  - Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. 
      Magrassi e A. Lanzara", Universita degli Studi della Campania Luigi Vanvitelli, 
      Via S. Pansini 5, 80131 Napoli, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20161230
PL  - Netherlands
TA  - Cancer Treat Rev
JT  - Cancer treatment reviews
JID - 7502030
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Colorectal Neoplasms/drug therapy
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - ErbB Receptors/*metabolism
MH  - Humans
MH  - Lung Neoplasms/drug therapy
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/metabolism
MH  - MAP Kinase Kinase 2/antagonists & inhibitors/metabolism
MH  - Metabolic Networks and Pathways/drug effects
MH  - Molecular Targeted Therapy/*methods
MH  - Mutation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins B-raf/genetics/metabolism
MH  - raf Kinases/*metabolism
MH  - ras Proteins/*metabolism
OTO - NOTNLM
OT  - CRC
OT  - MEK
OT  - NSCLC
OT  - Resistance
EDAT- 2017/01/11 06:00
MHDA- 2017/02/12 06:00
CRDT- 2017/01/11 06:00
PHST- 2016/09/08 00:00 [received]
PHST- 2016/11/30 00:00 [revised]
PHST- 2016/12/06 00:00 [accepted]
PHST- 2017/01/11 06:00 [pubmed]
PHST- 2017/02/12 06:00 [medline]
PHST- 2017/01/11 06:00 [entrez]
AID - S0305-7372(16)30142-6 [pii]
AID - 10.1016/j.ctrv.2016.12.001 [doi]
PST - ppublish
SO  - Cancer Treat Rev. 2017 Feb;53:61-69. doi: 10.1016/j.ctrv.2016.12.001. Epub 2016 
      Dec 30.