Is There a Role for Dual PI3K/mTOR Inhibitors for Patients Affected with Lymphoma?

Antineoplastic Agents / therapeutic use Cell Line, Tumor Cell Proliferation / drug effects Chromones / therapeutic use Humans Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy Lymphoma / drug therapy Molecular Targeted Therapy Oligopeptides / therapeutic use Phosphatidylinositol 3-Kinases / drug effects Phosphoinositide-3 Kinase Inhibitors / therapeutic use Proto-Oncogene Proteins c-akt / metabolism Quinoxalines / therapeutic use Signal Transduction / drug effects Sulfonamides / therapeutic use TOR Serine-Threonine Kinases / antagonists & inhibitors
PI3K TORC1 TORC2 chronic lymphocytic leukemia lymphoma

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
05 Feb 2020
Historique:
received: 21 01 2020
revised: 31 01 2020
accepted: 03 02 2020
entrez: 9 2 2020
pubmed: 9 2 2020
medline: 18 11 2020
Statut: epublish

Résumé

The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti-cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical responses, including complete remissions (especially in follicular lymphoma patients), are also observed in the very few clinical studies performed in patients that are affected by relapsed/refractory lymphomas or chronic lymphocytic leukemia. In this review, we summarize the literature on dual PI3K/mTOR inhibitors focusing on the lymphoma setting, presenting both the three compounds still in clinical development and those with a clinical program stopped or put on hold.

Identifiants

DOI: 10.3390/ijms21031060 PMID: 32033478 PMC: PMC7037719
pubmed: 32033478
pii: ijms21031060
doi: 10.3390/ijms21031060
pmc: PMC7037719
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Chromones 0
Oligopeptides 0
Phosphoinositide-3 Kinase Inhibitors 0
Quinoxalines 0
SF 1126 0
Sulfonamides 0
XL765 0
MTOR protein, human EC 2.7.1.1
Proto-Oncogene Proteins c-akt EC 2.7.11.1
TOR Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Déclaration de conflit d'intérêts

A.L.: part-time employee of Net4Science. A.S.: institutional research funds from: Bayer, ImmunoGen, Merck, Pfizer, Novartis, Roche; travel grant from AbbVie. F.B.: institutional research funds from Acerta, ADC Therapeutics, Bayer AG, Cellestia, CTI Life Sciences, EMD Serono, Helsinn, ImmunoGen, Menarini Ricerche, NEOMED Therapeutics 1, Oncology Therapeutic Development, PIQUR Therapeutics AG; consultancy fee from Helsinn, Menarini; expert statements provided to HTG; travel grants from Amgen, Astra Zeneca, Janssen-Cilag AG, Jazz Pharmaceuticals, PIQUR Therapeutics AG. The other co-authors do not report any conflict of interest.

Références

Leuk Lymphoma. 2013 Jun;54(6):1159-64
pubmed: 23013295
Mol Cancer Ther. 2011 Dec;10(12):2426-36
pubmed: 21998291
Int J Mol Sci. 2019 Aug 26;20(17):
pubmed: 31454887
Front Pharmacol. 2016 Oct 25;7:395
pubmed: 27826244
Cancers (Basel). 2018 Jan 25;10(2):
pubmed: 29370086
Nat Rev Drug Discov. 2009 Aug;8(8):627-44
pubmed: 19644473
Cancer Biol Ther. 2015;16(4):580-8
pubmed: 25793663
Nucleic Acids Res. 2019 Jan 8;47(D1):D1102-D1109
pubmed: 30371825
Clin Cancer Res. 2018 Jan 1;24(1):120-129
pubmed: 29066507
Diagn Mol Pathol. 2008 Sep;17(3):159-65
pubmed: 18382359
Oncotarget. 2012 Apr;3(4):371-94
pubmed: 22564882
Cancer Chemother Pharmacol. 2019 Feb;83(2):289-299
pubmed: 30446785
Clin Epigenetics. 2018 Jun 19;10:83
pubmed: 29951132
Nat Rev Cancer. 2015 Jan;15(1):7-24
pubmed: 25533673
Int J Oncol. 2016 Jan;48(1):253-60
pubmed: 26549638
EMBO J. 1995 Jul 17;14(14):3339-48
pubmed: 7628435
Invest New Drugs. 2016 Dec;34(6):740-749
pubmed: 27450049
Biomed Res Int. 2015;2015:870918
pubmed: 26557706
Clin Cancer Res. 2014 May 1;20(9):2445-56
pubmed: 24583798
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1289-94
pubmed: 16432180
Mol Cancer Ther. 2014 May;13(5):1078-91
pubmed: 24634413
Lancet Haematol. 2018 Apr;5(4):e170-e180
pubmed: 29550382
Biochem Soc Trans. 2014 Aug;42(4):733-41
pubmed: 25109950
J Exp Clin Cancer Res. 2016 Mar 24;35:52
pubmed: 27009084
Drugs. 2019 Aug;79(12):1287-1304
pubmed: 31313099
Blood. 2014 Feb 6;123(6):905-13
pubmed: 24363397
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Mol Cancer. 2019 Feb 19;18(1):26
pubmed: 30782187
Clin Cancer Res. 2009 Sep 15;15(18):5724-32
pubmed: 19723646
Cancer Chemother Pharmacol. 2019 Aug;84(2):337-343
pubmed: 31190275
Brain Dev. 2009 Jan;31(1):69-74
pubmed: 18538520
Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12420-5
pubmed: 23840064
Target Oncol. 2017 Dec;12(6):775-785
pubmed: 29067643
ACS Chem Biol. 2014 Feb 21;9(2):495-502
pubmed: 24533473
J Clin Invest. 2008 Sep;118(9):3065-74
pubmed: 18725988
Leukemia. 2007 Nov;21(11):2368-70
pubmed: 17657213
BMC Cancer. 2014 Aug 05;14:565
pubmed: 25096023
Invest New Drugs. 2014 Jun;32(3):510-7
pubmed: 24395457
J Clin Oncol. 2010 Feb 20;28(6):1075-83
pubmed: 20085938
Cancer J. 2012 Sep-Oct;18(5):404-10
pubmed: 23006944
J Thorac Oncol. 2014 Mar;9(3):316-23
pubmed: 24496004
Nat Genet. 2012 Dec;44(12):1321-5
pubmed: 23143597
Genes Dev. 2004 Aug 15;18(16):1926-45
pubmed: 15314020
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):802-7
pubmed: 15647370
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2349-54
pubmed: 24469833
J Med Chem. 2017 Sep 14;60(17):7524-7538
pubmed: 28829592
Haematologica. 2020 May;105(5):1361-1368
pubmed: 31471373
Leuk Lymphoma. 2015 Jan;56(1):263-6
pubmed: 24766470
Invest New Drugs. 2015 Apr;33(2):463-71
pubmed: 25707361
Cancer Treat Rev. 2017 Sep;59:93-101
pubmed: 28779636
Int J Mol Sci. 2018 Aug 19;19(8):
pubmed: 30126252
Nat Rev Mol Cell Biol. 2010 May;11(5):329-41
pubmed: 20379207
Cancer Discov. 2011 Dec;1(7):562-72
pubmed: 22586681
Leukemia. 2016 Feb;30(2):337-45
pubmed: 26338274
Clin Cancer Res. 2011 May 15;17(10):3193-203
pubmed: 21325073
Molecules. 2016 Nov 11;21(11):
pubmed: 27845732
Expert Opin Investig Drugs. 2012 Nov;21(11):1597-606
pubmed: 22920938
Oncotarget. 2015 Nov 3;6(34):35202-17
pubmed: 26460954
Clin Cancer Res. 2016 Apr 15;22(8):1932-9
pubmed: 26603258
Drug Deliv. 2018 Nov;25(1):668-678
pubmed: 29482386
Cell Death Dis. 2015 Jan 15;6:e1593
pubmed: 25590803
Breast Cancer Res Treat. 2015 Nov;154(2):287-97
pubmed: 26497877
Blood. 2013 Mar 21;121(12):2274-84
pubmed: 23341541
Clin Cancer Res. 2019 Jun 1;25(11):3374-3383
pubmed: 30796030
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13520-5
pubmed: 18765795
Nature. 2012 Oct 4;490(7418):116-20
pubmed: 22885699
J Cell Sci Suppl. 1994;18:121-6
pubmed: 7533766
Cancer Cell. 2018 Oct 8;34(4):549-560.e9
pubmed: 30300578
Neuropsychopharmacology. 2013 Jun;38(7):1143-53
pubmed: 23385661
Cell. 2017 Aug 10;170(4):605-635
pubmed: 28802037
Leuk Lymphoma. 2009 May;50(5):829-30
pubmed: 19330652
Science. 2004 Apr 23;304(5670):554
pubmed: 15016963
Cell. 2017 Mar 9;168(6):960-976
pubmed: 28283069
Oncologist. 2017 May;22(5):503-e43
pubmed: 28314838
J Med Chem. 2010 Mar 25;53(6):2636-45
pubmed: 20166697
Oncogene. 2016 Sep 29;35(39):5119-31
pubmed: 26999641
Chembiochem. 2012 Sep 24;13(14):2022-35
pubmed: 22965647
Mol Cancer Ther. 2011 Mar;10(3):395-403
pubmed: 21216931
Clin Cancer Res. 2015 Apr 15;21(8):1888-95
pubmed: 25652454
Leuk Res. 2012 Jul;36(7):912-20
pubmed: 22560334
Cancer Res. 2008 Jan 1;68(1):206-15
pubmed: 18172313
Cancer Lett. 2017 Apr 28;392:9-16
pubmed: 28159681
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):359-64
pubmed: 11756681
Oncologist. 2016 Jul;21(7):787-8
pubmed: 27286790
Future Oncol. 2018 Mar;14(7):665-674
pubmed: 29219001
Nat Rev Clin Oncol. 2018 May;15(5):273-291
pubmed: 29508857
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1475-9
pubmed: 16432179
Cancer Cell. 2017 Jun 12;31(6):820-832.e3
pubmed: 28528867
Nature. 1999 Sep 2;401(6748):86-90
pubmed: 10485711
Recent Results Cancer Res. 2016;207:39-72
pubmed: 27557534
Ann Oncol. 2012 Sep;23(9):2399-2408
pubmed: 22357447
Oncotarget. 2012 Oct;3(10):1068-111
pubmed: 23085539
Semin Cancer Biol. 2018 Feb;48:91-103
pubmed: 28467889
Leuk Lymphoma. 2010 Sep;51(9):1692-8
pubmed: 20807096
Eur J Cancer. 2012 Dec;48(18):3319-27
pubmed: 22921184
Leukemia. 2010 Oct;24(10):1781-4
pubmed: 20703254
Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954
pubmed: 27899562
J Med Chem. 2013 Mar 14;56(5):1922-39
pubmed: 23410005
Blood. 2019 Mar 21;133(12):1313-1324
pubmed: 30617194
Cancer Chemother Pharmacol. 2013 Apr;71(4):867-81
pubmed: 23355037
Pharmacol Rev. 2012 Oct;64(4):1027-54
pubmed: 23023033
Clin Cancer Res. 2014 Sep 15;20(18):4849-60
pubmed: 25070836
Eur J Cancer. 2018 Jun;96:6-16
pubmed: 29660598
Cancer Res. 2008 Oct 1;68(19):8022-30
pubmed: 18829560
Clin Cancer Res. 2016 Jun 15;22(12):2874-84
pubmed: 26787751
Cancer Res. 2006 Feb 1;66(3):1500-8
pubmed: 16452206
Eur J Cancer. 2017 May;76:36-44
pubmed: 28282611
Clin Cancer Res. 2013 Mar 1;19(5):1106-15
pubmed: 23300274
Gynecol Oncol. 2016 Jul;142(1):62-69
pubmed: 27103175
Cancer Chemother Pharmacol. 2018 Aug;82(2):285-298
pubmed: 29882016
Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):1624-9
pubmed: 26811457
ACS Med Chem Lett. 2016 Feb 16;7(4):351-6
pubmed: 27096040
Cell Metab. 2007 Apr;5(4):237-52
pubmed: 17403369
Cancer Treat Rev. 2018 Apr;65:87-95
pubmed: 29635163
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1398-403
pubmed: 23292937
Cancer Lett. 2013 Oct 10;339(2):288-97
pubmed: 23200668
J Chem Inf Model. 2015 Nov 23;55(11):2324-37
pubmed: 26479676
EMBO Mol Med. 2013 Apr;5(4):563-71
pubmed: 23483710
Haematologica. 2019 Jun;104(6):e256-e259
pubmed: 30545928
Front Immunol. 2018 Mar 27;9:578
pubmed: 29662490
JAMA Oncol. 2016 Dec 01;2(12):1565-1573
pubmed: 27388585
Blood. 2017 Aug 24;130(8):995-1006
pubmed: 28646116
Blood. 2019 Nov 7;134(19):1598-1607
pubmed: 31558468
Blood. 2006 Dec 15;108(13):4178-86
pubmed: 16946303
J Hematol Oncol. 2016 Aug 23;9(1):72
pubmed: 27554093
Br J Haematol. 2016 Oct;175(1):55-65
pubmed: 27293194
Cancer Discov. 2016 Oct;6(10):1090-1105
pubmed: 27655435
Curr Med Chem. 2011;18(36):5528-44
pubmed: 22172063
Clin Cancer Res. 2012 Jul 15;18(14):3791-802
pubmed: 22623730
Nat Immunol. 2014 Jan;15(1):88-97
pubmed: 24165795
Nature. 2007 Jul 26;448(7152):439-44
pubmed: 17611497
Invest New Drugs. 2018 Feb;36(1):36-44
pubmed: 28417284
Cell Metab. 2006 May;3(5):355-66
pubmed: 16679293
Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082
pubmed: 29126136
Clin Cancer Res. 2020 Apr 15;26(8):1820-1828
pubmed: 31937616
Target Oncol. 2017 Jun;12(3):323-332
pubmed: 28357727
Trends Mol Med. 2007 Jun;13(6):252-9
pubmed: 17452018
Blood. 2017 Jan 12;129(2):177-187
pubmed: 27777238
Oncotarget. 2016 Feb 23;7(8):9163-74
pubmed: 26824321
Leuk Lymphoma. 2015 Jun;56(6):1763-70
pubmed: 25300944
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15547-52
pubmed: 20713702

Auteurs

Chiara Tarantelli (C)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, Switzerland.

Antonio Lupia (A)

Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy.

Anastasios Stathis (A)

Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland.
Faculty of Biomedical Sciences, USI, 6900 Lugano, Switzerland.

Francesco Bertoni (F)

Institute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, Switzerland.
Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzopyranes › 4H-1-Benzopyran-4-ones › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Leucémie chronique lymphocytaire à cellules B › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Thérapie moléculaire ciblée › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Oligopeptides › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs des phosphoinositide-3 kinases › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-akt › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Quinoxalines › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Sulfones › Sulfonamides › Is There a Role for Dual PI3K/mTOR Inhibitors...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Is There a Role for Dual PI3K/mTOR Inhibitors...