PMID- 24063423
OWN - NLM
STAT- MEDLINE
DCOM- 20140617
LR  - 20220317
IS  - 1876-1038 (Electronic)
IS  - 1574-8871 (Linking)
VI  - 8
IP  - 2
DP  - 2013 Jun
TI  - Selumetinib in advanced non small cell lung cancer (NSCLC) harbouring KRAS 
      mutation: endless clinical challenge to KRAS-mutant NSCLC.
PG  - 93-100
AB  - During the past few years, oncologists have witnessed the reclassification of non 
      small cell lung cancer (NSCLC) as not one disease, but several molecularly 
      defined subsets of disease with relevant therapeutic implications in the field of 
      molecularly targeted therapies. Two not very common genetically defined subsets 
      of NSCLC, including those with EGFR or ALK activating mutations, and show high 
      sensitivity to tyrosine-kinase inhibitors such that patients frequently have 
      sustained clinical responses to therapy. However, the largest subset harbours an 
      activating KRAS mutation and up to now, no successful targeted therapy has been 
      developed for RAS-mutant lung cancer, with few compounds being assessed by 
      clinical trials. In fact, KRAS has remained an elusive target for cancer therapy 
      for biologic reasons. The chief value of KRAS lies in providing information about 
      the other biomarkers that are directly druggable, that is, EGFR and ALK. The 
      presence of mutated KRAS rules out ALK and EGFR, and KRAS may therefore form part 
      of an efficient pathway in a testing algorithm. Currently, KRAS itself remains 
      undruggable despite decades of effort, but attention has recently focused on 
      inhibition of the Ras-contingent downstream signalling. Selumetinib (AZD6244; 
      ARRY-142886) is an oral, tight-binding, uncompetitive inhibitor of 
      mitogen-activated protein kinase kinases (MEK) 1 and 2, downstream of KRAS, with 
      preclinical evidence of synergistic activity with docetaxel in KRAS-mutant 
      cancers and currently in clinical development. The Ras/RAF/MEK/ERK pathway is 
      frequently deregulated in cancer and a number of inhibitors that target this 
      pathway are currently in clinical development. Recently, in a randomised, phase 
      II trial selumetinib plus docetaxel has proven to improve progression free 
      survival compared to docetaxel alone in previously treated patients with advanced 
      KRAS-mutant NSCLC.
FAU - Paolo, Maione
AU  - Paolo M
AD  - Division of Medical Oncology, "S.G. Moscati" Hospital, Contrada Amoretta - 83100 
      Avellino Italy. cgridelli@libero.it.
FAU - Assunta, Sgambato
AU  - Assunta S
FAU - Antonio, Rossi
AU  - Antonio R
FAU - Claudia, Sacco Paola
AU  - Claudia SP
FAU - Anna, Bareschino Maria
AU  - Anna BM
FAU - Clorinda, Schettino
AU  - Clorinda S
FAU - Francesca, Casaluce
AU  - Francesca C
FAU - Fortunato, Ciardiello
AU  - Fortunato C
FAU - Cesare, Gridelli
AU  - Cesare G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Rev Recent Clin Trials
JT  - Reviews on recent clinical trials
JID - 101270873
RN  - 0 (AZD 6244)
RN  - 0 (Benzimidazoles)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Benzimidazoles/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/*genetics
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics
MH  - *Mutation
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - ras Proteins/*genetics
EDAT- 2013/09/26 06:00
MHDA- 2014/06/18 06:00
CRDT- 2013/09/26 06:00
PHST- 2013/05/07 00:00 [received]
PHST- 2013/07/22 00:00 [revised]
PHST- 2013/07/23 00:00 [accepted]
PHST- 2013/09/26 06:00 [entrez]
PHST- 2013/09/26 06:00 [pubmed]
PHST- 2014/06/18 06:00 [medline]
AID - RRCT-EPUB-54447 [pii]
AID - 10.2174/15748871113089990047 [doi]
PST - ppublish
SO  - Rev Recent Clin Trials. 2013 Jun;8(2):93-100. doi: 10.2174/15748871113089990047.