Esophageal carcinoma: Towards targeted therapies.
Adenocarcinoma
/ drug therapy
Antibodies, Monoclonal, Humanized
/ therapeutic use
Carcinoma, Squamous Cell
/ drug therapy
Cyclin-Dependent Kinase 4
/ antagonists & inhibitors
Cyclin-Dependent Kinase 6
/ antagonists & inhibitors
Enzyme Inhibitors
/ therapeutic use
Esophageal Neoplasms
/ drug therapy
Humans
Molecular Targeted Therapy
/ methods
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Clinical outcomes
Esophageal carcinoma
Molecular pathways
Precision medicine
Targeted therapies
Journal
Cellular oncology (Dordrecht)
ISSN: 2211-3436
Titre abrégé: Cell Oncol (Dordr)
Pays: Netherlands
ID NLM: 101552938
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
accepted:
22
11
2019
pubmed:
19
12
2019
medline:
15
12
2020
entrez:
19
12
2019
Statut:
ppublish
Résumé
Patients with esophageal cancer are confronted with high mortality rates. Whether it is esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC), patients usually present at advanced stages, with treatment options traditionally involving chemotherapy in metastatic settings. With the comprehensive genomic characterization of esophageal cancers, targeted therapies are gaining interest and agents such as ramucirumab, trastuzumab and pembrolizumab are already being used for the treatment of EAC. Pembrolizumab has recently been FDA-approved for PD-L1 positive, locally advanced or metastatic ESCC. Despite comprehensive molecular characterization, however, available targed therapies for ESCC are still lagging behind. Herein, we discuss current trends towards more targeted therapies in esophageal cancers, taking into consideration unique features of ESCCs and EACs. Patients progressing on standard therapies should be subjected to genomic profiling and considered for clinical trials aimed at testing targeted therapies. Future targeted therapies may include CDK4/6 inhibitors, PARP inhibitors and inhibitors targeting the NRF2 and Wnt signaling pathways. Ultimately, optimized biomarker assays and next generation sequencing platforms may allow for the identification of subcategories of ESCC and EAC patients that will benefit from selective targeted therapies and/or combinations thereof.
Sections du résumé
BACKGROUND
BACKGROUND
Patients with esophageal cancer are confronted with high mortality rates. Whether it is esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC), patients usually present at advanced stages, with treatment options traditionally involving chemotherapy in metastatic settings. With the comprehensive genomic characterization of esophageal cancers, targeted therapies are gaining interest and agents such as ramucirumab, trastuzumab and pembrolizumab are already being used for the treatment of EAC.
CONCLUSIONS
CONCLUSIONS
Pembrolizumab has recently been FDA-approved for PD-L1 positive, locally advanced or metastatic ESCC. Despite comprehensive molecular characterization, however, available targed therapies for ESCC are still lagging behind. Herein, we discuss current trends towards more targeted therapies in esophageal cancers, taking into consideration unique features of ESCCs and EACs. Patients progressing on standard therapies should be subjected to genomic profiling and considered for clinical trials aimed at testing targeted therapies. Future targeted therapies may include CDK4/6 inhibitors, PARP inhibitors and inhibitors targeting the NRF2 and Wnt signaling pathways. Ultimately, optimized biomarker assays and next generation sequencing platforms may allow for the identification of subcategories of ESCC and EAC patients that will benefit from selective targeted therapies and/or combinations thereof.
Identifiants
pubmed: 31848929
doi: 10.1007/s13402-019-00488-2
pii: 10.1007/s13402-019-00488-2
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Enzyme Inhibitors
0
Programmed Cell Death 1 Receptor
0
pembrolizumab
DPT0O3T46P
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Cyclin-Dependent Kinase 6
EC 2.7.11.22
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-209Références
Cell Oncol (Dordr). 2019 Apr;42(2):237-242
pubmed: 30680705
Commun Biol. 2018 Oct 24;1:174
pubmed: 30374464
Neoplasia. 2011 Sep;13(9):864-73
pubmed: 21969819
Lancet Oncol. 2014 Oct;15(11):1224-35
pubmed: 25240821
Clin Cancer Res. 2017 Oct 1;23(19):5671-5678
pubmed: 28655793
Lancet. 2010 Aug 28;376(9742):687-97
pubmed: 20728210
J Clin Oncol. 2016 Feb 10;34(5):443-51
pubmed: 26628478
Lancet Oncol. 2017 May;18(5):640-653
pubmed: 28343975
Ann Oncol. 2019 Aug 1;30(8):1232-1243
pubmed: 31056702
Nat Genet. 2013 May;45(5):478-86
pubmed: 23525077
Lancet. 2017 Nov 25;390(10110):2383-2396
pubmed: 28648400
Cell Oncol (Dordr). 2019 Oct;42(5):645-661
pubmed: 31147963
Nat Commun. 2017 Nov 16;8(1):1533
pubmed: 29142225
Expert Opin Ther Targets. 2007 Mar;11(3):375-89
pubmed: 17298295
Eur J Cancer. 2014 May;50(7):1247-58
pubmed: 24495747
Carcinogenesis. 2015 May;36(5):598-606
pubmed: 25795715
J Exp Med. 2013 Jul 29;210(8):1529-44
pubmed: 23857982
Ann Surg Oncol. 2014 Jul;21(7):2347-52
pubmed: 24599410
Nature. 2017 Jan 12;541(7636):169-175
pubmed: 28052061
Nat Genet. 2003 Nov;35(3):238-45
pubmed: 14517554
Esophagus. 2019 Jan;16(1):25-43
pubmed: 30171414
Gastroenterology. 2016 May;150(5):1171-1182
pubmed: 26873401
Am J Hum Genet. 2016 Feb 4;98(2):256-74
pubmed: 26833333
Nat Rev Dis Primers. 2017 Jul 27;3:17048
pubmed: 28748917
Esophagus. 2019 Jan;16(1):1-24
pubmed: 30171413
Lancet. 2014 Jan 4;383(9911):31-39
pubmed: 24094768
Nat Genet. 2016 Oct;48(10):1131-41
pubmed: 27595477
Ann N Y Acad Sci. 2018 Dec;1434(1):164-172
pubmed: 29752726
JAMA Oncol. 2019 Apr 1;5(4):546-550
pubmed: 30570649
Am J Hum Genet. 2015 Apr 2;96(4):597-611
pubmed: 25839328
Neoplasia. 2015 Jul;17(7):598-611
pubmed: 26297437
J Clin Oncol. 2018 Oct 1;36(28):2836-2844
pubmed: 30110194
Gastroenterology. 2018 Jan;154(2):360-373
pubmed: 28823862
Nat Rev Clin Oncol. 2018 Sep;15(9):564-576
pubmed: 29955114
J Pathol. 2012 Sep;228(1):99-112
pubmed: 22653845
Lancet Oncol. 2018 Oct;19(10):1372-1384
pubmed: 30217672
Nat Commun. 2019 Apr 11;10(1):1670
pubmed: 30975989
N Engl J Med. 2017 Nov 2;377(18):1792-3
pubmed: 29091556
J Surg Oncol. 2014 Oct;110(5):599-610
pubmed: 25146593
Cell Oncol (Dordr). 2019 Oct;42(5):609-626
pubmed: 31201647
Front Genet. 2019 Feb 18;10:47
pubmed: 30833958
J Gastrointest Oncol. 2017 Jun;8(3):418-429
pubmed: 28736629
Onco Targets Ther. 2016 Oct 19;9:6435-6444
pubmed: 27799791
Nat Genet. 2014 Oct;46(10):1097-102
pubmed: 25151357
BMC Syst Biol. 2014 Dec 31;8:1338
pubmed: 25551281
Ann Oncol. 2016 Sep;27(suppl 5):v50-v57
pubmed: 27664261
Anticancer Res. 2019 Apr;39(4):1813-1820
pubmed: 30952721
N Engl J Med. 1996 Aug 15;335(7):462-7
pubmed: 8672151
Ann Oncol. 2018 Oct 1;29(10):2052-2060
pubmed: 30052729
Nat Commun. 2017 May 26;8:15290
pubmed: 28548104
Ann Surg. 2000 Sep;232(3):353-61
pubmed: 10973385
Curr Oncol. 2018 Jun;25(3):e209-e216
pubmed: 29962847
Nat Genet. 2014 May;46(5):467-73
pubmed: 24686850
J Natl Compr Canc Netw. 2019 Jul 1;17(7):855-883
pubmed: 31319389
J Clin Oncol. 2008 Mar 1;26(7):1086-92
pubmed: 18309943
BMC Cancer. 2019 May 24;19(1):494
pubmed: 31126258
Nature. 2014 May 1;509(7498):91-5
pubmed: 24670651
Ann Oncol. 2019 Feb 1;30(2):250-258
pubmed: 30566590
Asian J Surg. 2018 May;41(3):210-215
pubmed: 27986415
Br J Pharmacol. 2017 Aug;174(15):2427-2443
pubmed: 28444744
Front Oncol. 2018 Dec 12;8:608
pubmed: 30631751
JAMA. 1999 May 5;281(17):1623-7
pubmed: 10235156
Oncol Res. 2012;20(2-3):123-30
pubmed: 23193918
Ann Cardiothorac Surg. 2017 Mar;6(2):119-130
pubmed: 28447000
Am J Hum Genet. 2016 Apr 7;98(4):709-27
pubmed: 27058444
Lancet Oncol. 2015 Sep;16(9):1090-1098
pubmed: 26254683
Lancet Oncol. 2007 Mar;8(3):226-34
pubmed: 17329193
Lancet Oncol. 2013 May;14(6):481-9
pubmed: 23594787
Exp Hematol Oncol. 2018 Nov 16;7:28
pubmed: 30473928
J Gastroenterol. 2019 Aug;54(8):687-698
pubmed: 30737573
Oncotarget. 2017 Jul 25;8(30):49851-49860
pubmed: 28591712
Lancet. 2018 Jul 14;392(10142):123-133
pubmed: 29880231
JAMA Oncol. 2018 May 10;4(5):e180013
pubmed: 29543932
Nat Genet. 2019 Mar;51(3):506-516
pubmed: 30718927
Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):134-47
pubmed: 22144499
Oncologist. 2019 Jan;24(1):103-109
pubmed: 30120163
N Engl J Med. 2018 Aug 23;379(8):753-763
pubmed: 30110579
Lancet. 2017 Dec 2;390(10111):2461-2471
pubmed: 28993052
Oncogene. 2017 Apr 20;36(16):2243-2254
pubmed: 27819679
Thorac Cancer. 2018 Jun;9(6):726-735
pubmed: 29675925