The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells.
Dose-Response Relationship, Radiation
Head and Neck Neoplasms
/ metabolism
Humans
Phosphatidylinositol 3-Kinases
/ chemistry
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
Radiation Tolerance
/ drug effects
Radiation-Sensitizing Agents
/ pharmacology
Signal Transduction
Squamous Cell Carcinoma of Head and Neck
/ metabolism
Tumor Cells, Cultured
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
04
05
2020
accepted:
07
08
2020
entrez:
2
10
2020
pubmed:
3
10
2020
medline:
13
1
2021
Statut:
epublish
Résumé
Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited.
Identifiants
pubmed: 33004905
doi: 10.1038/s41598-020-73249-z
pii: 10.1038/s41598-020-73249-z
pmc: PMC7529775
doi:
Substances chimiques
Phosphoinositide-3 Kinase Inhibitors
0
Radiation-Sensitizing Agents
0
Banques de données
ClinicalTrials.gov
['NCT02113878']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16208Références
Nature. 2015 Jan 29;517(7536):576-82
pubmed: 25631445
Clin Cancer Res. 2018 Jun 1;24(11):2505-2516
pubmed: 29490986
Cancer Res. 2014 Mar 15;74(6):1739-51
pubmed: 24473065
Head Neck. 2017 Jan;39(1):151-159
pubmed: 27507562
Lancet Oncol. 2008 Mar;9(3):288-96
pubmed: 18308254
Nat Rev Drug Discov. 2011 Aug 01;10(8):563-4
pubmed: 21804582
Oncotarget. 2014 Jun 15;5(11):3662-72
pubmed: 25004403
Oncotarget. 2017 Mar 28;8(13):22203-22217
pubmed: 28108737
Mol Cancer Ther. 2017 Apr;16(4):729-738
pubmed: 28119490
Oncotarget. 2017 Sep 16;8(46):81662-81678
pubmed: 29113422
Clin Cancer Res. 2016 Apr 15;22(8):2009-19
pubmed: 26589432
Oral Oncol. 2015 Apr;51(4):291-8
pubmed: 25532816
Int J Mol Sci. 2017 Nov 20;18(11):
pubmed: 29156644
Breast Cancer (Dove Med Press). 2015 May 15;7:111-23
pubmed: 26028978
Mol Cancer Ther. 2012 Feb;11(2):317-28
pubmed: 22188813
Clin Cancer Res. 2014 Jan 1;20(1):110-9
pubmed: 24198241
Mol Cancer Ther. 2011 Dec;10(12):2426-36
pubmed: 21998291
Cancer Chemother Pharmacol. 2012 Jun;69(6):1601-15
pubmed: 22543857
J Oncol. 2012;2012:450179
pubmed: 22666248
Cancer Treat Rev. 2013 Jun;39(4):313-20
pubmed: 23218708
Radiother Oncol. 2014 Apr;111(1):72-80
pubmed: 24631147
Clin Cancer Res. 2012 Jan 1;18(1):184-95
pubmed: 22065080
N Engl J Med. 2001 Dec 27;345(26):1890-900
pubmed: 11756581
J Mol Diagn. 2013 May;15(3):312-8
pubmed: 23541593
Front Oncol. 2013 May 08;3:108
pubmed: 23658859
Clin Cancer Res. 2013 Jul 15;19(14):3808-19
pubmed: 23640975
Radiother Oncol. 2013 May;107(2):242-6
pubmed: 23602369
Expert Opin Ther Targets. 2015 Jun;19(6):795-805
pubmed: 25652792
Oncotarget. 2016 Oct 11;7(41):67277-67287
pubmed: 27572309
Semin Cancer Biol. 2015 Dec;35:180-90
pubmed: 26192967
Cancer Discov. 2013 Jul;3(7):761-9
pubmed: 23619167
Int J Cancer. 2013 Jul;133(1):247-52
pubmed: 23238639
J Natl Cancer Inst. 2007 May 16;99(10):777-89
pubmed: 17505073
Lancet Oncol. 2017 Mar;18(3):323-335
pubmed: 28131786
J Cancer Res Clin Oncol. 2014 Apr;140(4):573-82
pubmed: 24500492
Oncotarget. 2015 Sep 29;6(29):26995-7007
pubmed: 26336991
Cancer Res. 2018 Jun 1;78(11):3075-3086
pubmed: 29559471
Nat Commun. 2016 Apr 25;7:11428
pubmed: 27109210
Sci Rep. 2016 Sep 13;6:32992
pubmed: 27623107
Drug Metab Dispos. 2012 Sep;40(9):1785-96
pubmed: 22696419
Invest New Drugs. 2014 Dec;32(6):1134-43
pubmed: 25152245
Drugs. 2019 Jul;79(11):1249-1253
pubmed: 31256368
PLoS One. 2016 May 03;11(5):e0154745
pubmed: 27137757
Int J Biochem Cell Biol. 2016 Oct;79:308-317
pubmed: 27599915
Neoplasia. 2014 Jan;16(1):43-72
pubmed: 24563619
Oncotarget. 2016 Dec 20;7(51):84286-84298
pubmed: 27713179
Invest New Drugs. 2015 Apr;33(2):310-20
pubmed: 25603975
Oncotarget. 2017 May 2;8(18):29963-29975
pubmed: 28415784
Clin Transl Radiat Oncol. 2018 Apr 27;11:1-10
pubmed: 30014041
JAMA Otolaryngol Head Neck Surg. 2015 Jun;141(6):543-9
pubmed: 25855885
Otorhinolaryngol Head Neck Surg. 2016;1(2):44-50
pubmed: 28004037
Oncotarget. 2016 Jun 21;7(25):38785-38795
pubmed: 27246975
Nat Commun. 2017 Mar 09;8:14683
pubmed: 28276440
Clin Cancer Res. 2015 Jun 15;21(12):2792-801
pubmed: 25724523
Head Neck. 2015 May;37(5):763-70
pubmed: 24995469
Int J Cancer. 2020 Feb 15;146(4):1075-1085
pubmed: 31283004
J Clin Oncol. 2014 Sep 10;32(26):2886-93
pubmed: 25113770
Breast Cancer Res. 2014 Aug 08;16(4):406
pubmed: 25103565
Strahlenther Onkol. 2014 Sep;190(9):839-46
pubmed: 24715240
Cancers (Basel). 2016 Aug 05;8(8):
pubmed: 27527216
Nucleic Acids Res. 2017 Jan 4;45(D1):D777-D783
pubmed: 27899578
Cancer Manag Res. 2017 Aug 18;9:363-371
pubmed: 28860859
Eur J Cancer. 2019 May;113:87-95
pubmed: 30991262
Cancer Res. 2012 Jan 1;72(1):239-48
pubmed: 22108822
Clin Transl Oncol. 2016 Jun;18(6):541-9
pubmed: 26510854
Mol Cancer Ther. 2012 Aug;11(8):1747-57
pubmed: 22653967
Oncotarget. 2016 Sep 27;7(39):63106-63123
pubmed: 27527858
Anticancer Res. 2015 Jan;35(1):175-82
pubmed: 25550549
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Acta Pharmacol Sin. 2012 Dec;33(12):1441-58
pubmed: 22983389
Nat Rev Drug Discov. 2014 Feb;13(2):140-56
pubmed: 24481312
Sci Rep. 2018 Mar 2;8(1):3947
pubmed: 29500400
J Pharmacol Exp Ther. 2014 Jul;350(1):22-35
pubmed: 24741074
Cancer Res. 2013 Oct 15;73(20):6289-98
pubmed: 23980093