PMID- 27507562
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20191210
IS  - 1097-0347 (Electronic)
IS  - 1043-3074 (Linking)
VI  - 39
IP  - 1
DP  - 2017 Jan
TI  - Combination of phosphotidylinositol-3-kinase targeting with cetuximab and 
      irradiation: A preclinical study on an orthotopic xenograft model of head and 
      neck cancer.
PG  - 151-159
LID - 10.1002/hed.24560 [doi]
AB  - BACKGROUND: The purpose of this study was to investigate the effects of combining 
      the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the 
      anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy 
      (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC). 
      METHODS: We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, 
      administered alone or in combination, using the human PIK3CA-mutated HNSCC cell 
      line, CAL33, injected into the floor of the mouth of nude mice. RESULTS: Compared 
      with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led 
      to the highest tumor inhibition (p < .001). The highest inhibitory effect of 
      treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and 
      PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling 
      pathways were found with the BKM120-cetuximab association. The association of 
      BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway. 
      CONCLUSION: These results can serve as a preclinical rationale for innovative 
      treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in 
      patients with HNSCC. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 151-159, 2017.
CI  - (c) 2016 Wiley Periodicals, Inc.
FAU - Bozec, Alexandre
AU  - Bozec A
AD  - University Institute of the Face and Neck, Nice cedex, France.
FAU - Ebran, Nathalie
AU  - Ebran N
AD  - Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, 
      Nice cedex, France.
FAU - Radosevic-Robin, Nina
AU  - Radosevic-Robin N
AD  - Department of Pathology, Jean Perrin Comprehensive Cancer Centre, 
      Clermont-Ferrand, France.
AD  - ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.
FAU - Chamorey, Emmanuel
AU  - Chamorey E
AD  - Department of Clinical Research, Innovation and Statistics (DRIS), Antoine 
      Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
FAU - Yahia, Hedi Ben
AU  - Yahia HB
AD  - Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, 
      Nice cedex, France.
FAU - Marcie, Serge
AU  - Marcie S
AD  - Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice 
      cedex, France.
FAU - Gautier, Mathieu
AU  - Gautier M
AD  - Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice 
      cedex, France.
FAU - Penault-Llorca, Frederique
AU  - Penault-Llorca F
AD  - Department of Pathology, Jean Perrin Comprehensive Cancer Centre, 
      Clermont-Ferrand, France.
AD  - ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.
FAU - Milano, Gerard
AU  - Milano G
AD  - Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, 
      Nice cedex, France.
LA  - eng
PT  - Journal Article
DEP - 20160810
PL  - United States
TA  - Head Neck
JT  - Head & neck
JID - 8902541
RN  - 0 (Aminopyridines)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Morpholines)
RN  - 0 (NVP-BKM120)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Aminopyridines/*therapeutic use
MH  - Animals
MH  - Antineoplastic Agents, Immunological/*therapeutic use
MH  - Carcinoma, Squamous Cell/*drug therapy/pathology/*radiotherapy
MH  - Cetuximab/*therapeutic use
MH  - Combined Modality Therapy
MH  - Disease Models, Animal
MH  - Female
MH  - Head and Neck Neoplasms/*drug therapy/pathology/*radiotherapy
MH  - Mice
MH  - Mice, Nude
MH  - Morpholines/*therapeutic use
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Squamous Cell Carcinoma of Head and Neck
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - epidermal growth factor receptor (EGFR)
OT  - head and neck cancer
OT  - phosphatidylinositol 3-kinase (PIK3CA)
OT  - radiotherapy
OT  - targeted therapy
EDAT- 2016/08/11 06:00
MHDA- 2018/02/24 06:00
CRDT- 2016/08/11 06:00
PHST- 2016/01/25 00:00 [received]
PHST- 2016/03/24 00:00 [revised]
PHST- 2016/06/27 00:00 [accepted]
PHST- 2016/08/11 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2016/08/11 06:00 [entrez]
AID - 10.1002/hed.24560 [doi]
PST - ppublish
SO  - Head Neck. 2017 Jan;39(1):151-159. doi: 10.1002/hed.24560. Epub 2016 Aug 10.