The complex nature of heterogeneity and its roles in breast cancer biology and therapeutic responsiveness.
breast cancer
drug resistance
endocrine therapy
heterogeneity
systems biology
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
10
2022
accepted:
02
02
2023
entrez:
13
3
2023
pubmed:
14
3
2023
medline:
15
3
2023
Statut:
epublish
Résumé
Heterogeneity is a complex feature of cells and tissues with many interacting components. Depending on the nature of the research context, interacting features of cellular, drug response, genetic, molecular, spatial, temporal, and vascular heterogeneity may be present. We describe the various forms of heterogeneity with examples of their interactions and how they play a role in affecting cellular phenotype and drug responses in breast cancer. While cellular heterogeneity may be the most widely described and invoked, many forms of heterogeneity are evident within the tumor microenvironment and affect responses to the endocrine and cytotoxic drugs widely used in standard clinical care. Drug response heterogeneity is a critical determinant of clinical response and curative potential and also is multifaceted when encountered. The interactive nature of some forms of heterogeneity is readily apparent. For example, the process of metastasis has the properties of both temporal and spatial heterogeneity within the host, whereas each individual metastatic deposit may exhibit cellular, genetic, molecular, and vascular heterogeneity. This review describes the many forms of heterogeneity, their integrated activities, and offers some insights into how heterogeneity may be understood and studied in the future.
Identifiants
pubmed: 36909339
doi: 10.3389/fendo.2023.1083048
pmc: PMC9997040
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1083048Informations de copyright
Copyright © 2023 Andrade de Oliveira, Sengupta, Yadav and Clarke.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Mol Cell. 2019 Dec 5;76(5):838-851.e5
pubmed: 31564558
Nat Rev Clin Oncol. 2015 Oct;12(10):573-83
pubmed: 26122181
Nature. 2012 May 16;486(7403):400-4
pubmed: 22722201
J Clin Oncol. 2003 Sep 1;21(17):3357-65
pubmed: 12847142
Cell Stem Cell. 2015 Sep 3;17(3):260-71
pubmed: 26340526
Tumour Biol. 2016 Mar;37(3):2849-61
pubmed: 26797784
Proteomics. 2022 Oct;22(19-20):e2100256
pubmed: 35687565
Clin Cancer Res. 2021 Jan 15;27(2):504-512
pubmed: 33082214
Breast J. 1999 Nov;5(6):369-374
pubmed: 11348316
Nature. 2007 Mar 8;446(7132):153-8
pubmed: 17344846
Semin Cancer Biol. 2015 Apr;31:65-75
pubmed: 25117005
Front Oncol. 2019 Aug 02;9:686
pubmed: 31428575
Eur J Cancer Clin Oncol. 1984 Mar;20(3):375-82
pubmed: 6323188
MedGenMed. 2005 Aug 24;7(3):20
pubmed: 16369246
Breast Cancer Res. 2014 Jun 11;16(3):R62
pubmed: 24919951
Exp Cell Res. 2020 Jun 15;391(2):111983
pubmed: 32268136
Clin Cancer Res. 2020 Aug 1;26(15):3947-3957
pubmed: 32312891
Cancer Cell. 2018 Sep 10;34(3):427-438.e6
pubmed: 30205045
JAMA Oncol. 2020 Jan 01;6(1):116-124
pubmed: 31563959
N Engl J Med. 2019 May 16;380(20):1929-1940
pubmed: 31091374
Cancer Res. 2021 Jan 15;81(2):268-281
pubmed: 33148662
Front Oncol. 2022 May 13;12:876451
pubmed: 35646658
Clin Cancer Res. 2013 Dec 1;19(23):6389-97
pubmed: 24298069
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Cell Cycle. 2010 Aug 15;9(16):3256-76
pubmed: 20814239
Nat Commun. 2018 Dec 4;9(1):5150
pubmed: 30514914
BMC Cancer. 2019 Apr 11;19(1):351
pubmed: 30975104
Clin J Am Soc Nephrol. 2010 Feb;5(2):314-27
pubmed: 20056753
Oncologist. 2021 Jul;26(7):e1133-e1142
pubmed: 33909934
Nat Rev Cancer. 2017 Oct;17(10):605-619
pubmed: 28912577
Nat Commun. 2016 Aug 09;7:12498
pubmed: 27502118
Int J Dev Biol. 2011;55(7-9):841-9
pubmed: 22161840
Cell Stem Cell. 2012 Apr 6;10(4):440-54
pubmed: 22482508
Nat Rev Cancer. 2009 Aug;9(8):550-62
pubmed: 19629070
Cell. 2010 Apr 2;141(1):69-80
pubmed: 20371346
Metabolomics. 2022 Oct 1;18(10):77
pubmed: 36181583
PLoS One. 2019 Dec 10;14(12):e0226150
pubmed: 31821370
Front Endocrinol (Lausanne). 2021 Mar 25;12:599586
pubmed: 33841325
Cancer Lett. 2021 Apr 1;502:189-199
pubmed: 33278499
Lancet Oncol. 2020 Nov;21(11):1443-1454
pubmed: 33152284
Aging (Albany NY). 2021 Jun 28;13(12):16178-16197
pubmed: 34182538
NPJ Breast Cancer. 2022 Jun 29;8(1):76
pubmed: 35768433
Cell Rep. 2015 Sep 29;12(12):1968-77
pubmed: 26387946
Endocr Relat Cancer. 2006 Sep;13(3):739-49
pubmed: 16954428
Cell. 2012 May 25;149(5):979-93
pubmed: 22608084
J Adv Pract Oncol. 2021 Jan-Feb;12(1):100-107
pubmed: 33552665
Expert Opin Investig Drugs. 2010 Apr;19 Suppl 1:S41-50
pubmed: 20374029
Clin Cancer Res. 2004 Sep 1;10(17):5902-6
pubmed: 15355923
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
Trends Cell Biol. 2015 Apr;25(4):198-213
pubmed: 25540894
Breast Cancer Res Treat. 2014 Jan;143(1):113-24
pubmed: 24309997
Am J Pathol. 2009 Mar;174(3):746-61
pubmed: 19234134
Nature. 2019 May;569(7757):560-564
pubmed: 31118521
Ann Oncol. 2021 Feb;32(2):208-217
pubmed: 33246021
Cancers (Basel). 2021 Jun 01;13(11):
pubmed: 34206026
Nat Genet. 2013 Dec;45(12):1446-51
pubmed: 24185510
Cells. 2020 Dec 04;9(12):
pubmed: 33291749
J Natl Cancer Inst. 2009 Dec 16;101(24):1725-9
pubmed: 19940281
Mol Cell. 2015 May 21;58(4):610-20
pubmed: 26000846
Gene. 2018 Dec 15;678:302-311
pubmed: 30096458
Cell. 2018 Feb 8;172(4):841-856.e16
pubmed: 29395328
Oncogene. 2020 Jun;39(25):4896-4908
pubmed: 32472077
Expert Opin Ther Targets. 2010 Jul;14(7):681-92
pubmed: 20446866
J Exp Clin Cancer Res. 2021 Jan 11;40(1):28
pubmed: 33423689
Genome Med. 2022 Dec 7;14(1):137
pubmed: 36476325
N Engl J Med. 2019 Jul 25;381(4):307-316
pubmed: 31166679
Sci Rep. 2020 Dec 14;10(1):21933
pubmed: 33318536
Nat Commun. 2018 Nov 29;9(1):5079
pubmed: 30498242
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):802-7
pubmed: 15647370
Science. 2006 Oct 13;314(5797):268-74
pubmed: 16959974
Biochim Biophys Acta Rev Cancer. 2018 Dec;1870(2):123-136
pubmed: 30003999
PLoS One. 2015 Jul 09;10(7):e0132285
pubmed: 26158266
Cancer Cell. 2007 Aug;12(2):108-13
pubmed: 17692803
Clin Cancer Res. 2003 Jan;9(1 Pt 2):480S-5S
pubmed: 12538504
J Clin Oncol. 2005 Oct 1;23(28):7212-20
pubmed: 16192605
Clin Cancer Res. 2014 Apr 1;20(7):1724-6
pubmed: 24583794
Cancer Chemother Pharmacol. 2021 Feb;87(2):147-158
pubmed: 33420940
JAMA Oncol. 2016 Nov 01;2(11):1477-1486
pubmed: 27367583
Mol Cell. 2015 Nov 19;60(4):537-46
pubmed: 26590713
Nature. 2012 Jun 20;486(7403):405-9
pubmed: 22722202
Cancers (Basel). 2020 Oct 21;12(10):
pubmed: 33096662
Nat Rev Cancer. 2008 Jan;8(1):37-49
pubmed: 18097463
NMR Biomed. 2012 Nov;25(11):1234-44
pubmed: 22419606
Nat Genet. 2013 Dec;45(12):1439-45
pubmed: 24185512
J Proteome Res. 2022 Aug 5;21(8):1808-1815
pubmed: 35849481
Genome Biol. 2018 Dec 3;19(1):211
pubmed: 30509292
Front Oncol. 2018 Dec 21;8:646
pubmed: 30622930
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13820-5
pubmed: 19666588
Cancer Cell. 2020 Apr 13;37(4):471-484
pubmed: 32289271
Pharmacol Ther. 2018 Jun;186:1-24
pubmed: 29289555
Mol Cancer. 2014 Oct 23;13:239
pubmed: 25339305
Science. 2004 Apr 23;304(5670):554
pubmed: 15016963
Front Immunol. 2021 Dec 17;12:799428
pubmed: 34992609
Cell Metab. 2018 Nov 6;28(5):793-800.e2
pubmed: 30146487
J Clin Oncol. 2021 Oct 1;39(28):3171-3181
pubmed: 34357781
Biomark Res. 2020 Nov 11;8(1):64
pubmed: 33292666
Adv Exp Med Biol. 2016;882:169-89
pubmed: 26987535
Endocrinology. 2019 Aug 1;160(8):1811-1820
pubmed: 31157867
Adv Sci (Weinh). 2020 Sep 24;7(21):2002518
pubmed: 33173749
Oncotarget. 2015 Nov 17;6(36):39307-28
pubmed: 26515727
Front Oncol. 2017 Sep 04;7:184
pubmed: 28929082
Nat Cancer. 2021 Jun;2(6):658-671
pubmed: 34712959
Nat Cell Biol. 2020 Mar;22(3):310-320
pubmed: 32144411
Cancer. 1975 Jan;35(1):98-110
pubmed: 162854
Cancer Res. 2013 Dec 1;73(23):6856-64
pubmed: 24217577
Nat Commun. 2017 May 05;8:15081
pubmed: 28474673
Appl Immunohistochem Mol Morphol. 2010 Oct;18(5):433-41
pubmed: 20485156
Med Oncol. 2015 Feb;32(2):352
pubmed: 25572805
Genome Res. 2010 Jan;20(1):68-80
pubmed: 19903760
Breast Cancer Res. 2005;7(5):R753-64
pubmed: 16168121
Int J Breast Cancer. 2011;2011:232435
pubmed: 22295213
Biochim Biophys Acta Rev Cancer. 2021 Jan;1875(1):188488
pubmed: 33271308
Clin Cancer Res. 2014 Apr 1;20(7):1757-1767
pubmed: 24398047
Mol Cell Endocrinol. 2015 Dec 15;418 Pt 3:220-34
pubmed: 26455641
Lancet Oncol. 2022 Jul;23(7):851-864
pubmed: 35671774
Neoplasia. 2017 Oct;19(10):791-804
pubmed: 28869838
Lancet. 1992 Jan 4;339(8784):1-15
pubmed: 1345950
Trends Cancer. 2020 Jan;6(1):49-61
pubmed: 31952781
Semin Cell Dev Biol. 2020 May;101:111-114
pubmed: 31708414
J Cell Physiol. 2019 May;234(5):5700-5721
pubmed: 30378106
Front Endocrinol (Lausanne). 2021 Nov 03;12:687244
pubmed: 34803903
Oncol Lett. 2015 Apr;9(4):1495-1501
pubmed: 25788989
J Clin Oncol. 2016 Sep 1;34(25):3069-103
pubmed: 27217461
Nat Commun. 2017 Apr 20;8:14944
pubmed: 28429735
Semin Cancer Biol. 2022 Jan;78:49-62
pubmed: 33582172
Nat Commun. 2016 May 03;7:11246
pubmed: 27138336
J Pathol. 2012 Aug;227(4):490-8
pubmed: 22488553
Nat Genet. 2021 Sep;53(9):1334-1347
pubmed: 34493872
Cancer Cell. 2017 Aug 14;32(2):169-184.e7
pubmed: 28810143
Nat Med. 2015 Jul;21(7):751-9
pubmed: 26099045
Stem Cells Int. 2016;2016:2498764
pubmed: 26880941
Cancer Metastasis Rev. 2022 Jun;41(2):447-458
pubmed: 35419769
J Immunol. 2005 Jul 1;175(1):342-9
pubmed: 15972667
Cancer Discov. 2021 Apr;11(4):971-994
pubmed: 33811127
Nat Genet. 2022 Jun;54(6):850-860
pubmed: 35681052
Tumour Biol. 2015 Nov;36(11):8685-95
pubmed: 26044562
Cancers (Basel). 2021 Jul 14;13(14):
pubmed: 34298731
Cell Metab. 2019 Sep 3;30(3):434-446
pubmed: 31484055
Am J Surg. 2009 Oct;198(4):520-5
pubmed: 19800460
Nat Cell Biol. 2015 Apr;17(4):351-9
pubmed: 25774832
Cell Cycle. 2010 Sep 1;9(17):3515-33
pubmed: 20855962
Nat Commun. 2018 Sep 4;9(1):3588
pubmed: 30181541
Biochim Biophys Acta Rev Cancer. 2019 Dec;1872(2):188315
pubmed: 31647985
Lancet. 1998 May 16;351(9114):1451-67
pubmed: 9605801
Tumour Biol. 2014 Feb;35(2):1275-86
pubmed: 24014089
Breast Cancer Res Treat. 2013 Jun;139(2):539-52
pubmed: 23674192
Clin Chem. 2015 Dec;61(12):1457-65
pubmed: 26467503
Nat Commun. 2019 Sep 2;10(1):3840
pubmed: 31477698
Endocr Relat Cancer. 2008 Sep;15(3):755-63
pubmed: 18550720
Breast Cancer Res. 2013 Mar 08;15(2):R21
pubmed: 23497505
Clin Cancer Res. 2017 Apr 1;23(7):1710-1721
pubmed: 27702820
Pharmacol Res. 2021 Jan;163:105320
pubmed: 33271295
Front Oncol. 2020 Oct 22;10:566511
pubmed: 33194645
Breast Cancer Res Treat. 2012 Jun;133(2):459-71
pubmed: 21935603
Cancer Res. 2017 Apr 15;77(8):1927-1941
pubmed: 28202520
J Clin Oncol. 2013 Jun 10;31(17):2128-35
pubmed: 23650416
Ann Oncol. 2013 Jan;24(1):126-33
pubmed: 22865780
Br J Cancer. 1995 Jul;72(1):51-5
pubmed: 7599066
EMBO J. 2020 Oct 1;39(19):e104063
pubmed: 32790115
Cancer Discov. 2021 May;11(5):1286-1305
pubmed: 33328216
Immunity. 2014 Jul 17;41(1):49-61
pubmed: 25035953
PLoS Genet. 2011 Aug;7(8):e1002229
pubmed: 21852960
Clin Cancer Res. 2005 Jan 15;11(2 Pt 2):951s-8s
pubmed: 15701892
Cell Oncol (Dordr). 2021 Dec;44(6):1209-1229
pubmed: 34528143
Clin Pharmacokinet. 2005;44(1):61-98
pubmed: 15634032
Clin Cancer Res. 2007 Oct 1;13(19):5769-76
pubmed: 17908967
Breast Cancer Res Treat. 2022 Jan;191(2):257-267
pubmed: 34731350
Nat Med. 2021 Jan;27(1):34-44
pubmed: 33442008
Cancers (Basel). 2019 Feb 06;11(2):
pubmed: 30736340
JNCI Cancer Spectr. 2019 Aug 10;3(4):pkz049
pubmed: 32337478
Int J Biochem Cell Biol. 2019 Feb;107:38-52
pubmed: 30529656
Cell. 2012 May 25;149(5):994-1007
pubmed: 22608083
Pharmacogenomics. 2017 Jun;18(8):821-830
pubmed: 28592202
Pharmacogenomics. 2017 Apr;18(5):481-499
pubmed: 28346074
Breast Cancer Res Treat. 2020 Jan;179(1):67-77
pubmed: 31562570
Breast Cancer Res. 2020 Oct 15;22(1):107
pubmed: 33059724
Br J Cancer. 2001 Oct 19;85(8):1106-12
pubmed: 11710821
Cancers (Basel). 2020 May 21;12(5):
pubmed: 32455670
Nat Commun. 2020 Jan 21;11(1):404
pubmed: 31964880
Cell. 2015 Oct 8;163(2):506-19
pubmed: 26451490
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
Front Oncol. 2022 Aug 08;12:964934
pubmed: 36003773
Sci Rep. 2015 Jul 23;5:12465
pubmed: 26202299
Nat Commun. 2022 Mar 31;13(1):1714
pubmed: 35361816
Cell. 2016 Feb 11;164(4):681-94
pubmed: 26853473