Insights into breast cancer phenotying through molecular omics approaches and therapy response

Jose E. Belizario , Angela F. Loggulo

Cancer Drug Resistance ›› 2019, Vol. 2 ›› Issue (3) : 527 -538.

PDF
Cancer Drug Resistance ›› 2019, Vol. 2 ›› Issue (3) :527 -538. DOI: 10.20517/cdr.2018.009
Review
review-article

Insights into breast cancer phenotying through molecular omics approaches and therapy response

Author information +
History +
PDF

Abstract

Breast cancer is the most common cancer in the world. Despite advances in early detection and understanding of the molecular bases of breast cancer biology, approximately 30% of all patients with early-stage breast cancer have metastatic disease. Breast cancers are comprised of molecularly distinct subtypes that respond differently to pathway-targeted therapies and neoadjuvant systemic therapy. However, no tumor response is observed in some cases and development of resistance is most commonly seen in patients with heterogeneous breast cancer subtype. To offer better treatment with increased efficacy and low toxicity of selecting therapies, new technologies that incorporate clinical and molecular characteristics of intratumoral heterogeneity have been investigated. This short review provides some examples of integrative omics approaches (genome, epigenome, transcriptome, immune profiling) and mathematical/computational analyses that provide mechanistic and clinically relevant insights into underlying differences in breast cancer subtypes and patients’responses to specific therapies.

Keywords

Breast cancer / ERBB/HER / estrogen receptor / progesterone receptor / genomics / proteomics / epigenomics / endocrine and targeted therapy

Cite this article

Download citation ▾
Jose E. Belizario, Angela F. Loggulo. Insights into breast cancer phenotying through molecular omics approaches and therapy response. Cancer Drug Resistance, 2019, 2(3): 527-538 DOI:10.20517/cdr.2018.009

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Belizario JE.Cancer risks linked to the bad luck hypothesis and epigenomic mutational signatures..Epigenomes2018;2:13

[2]

Lawrence MS,Mermel CH,Garraway LA.Discovery and saturation analysis of cancer genes across 21 tumour types..Nature2014;505:495-501 PMCID:PMC4048962

[3]

Vasaikar SV,Wang J.LinkedOmics: analyzing multi-omics data within and across 32 cancer types..Nucleic Acids Res2018;46:D956-63 PMCID:PMC5753188

[4]

Kim YA,Przytycka TM.Understanding genotype - phenotype effects in cancer via network approaches..PLoS Comput Biol2016;12:e1004747 PMCID:PMC4786343

[5]

Barretina J,Stransky N,Margolin AA.The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity..Nature2012;483:603-7 PMCID:PMC3320027

[6]

Garnett MJ,Heidorn SJ,Dastur A.Systematic identification of genomic markers of drug sensitivity in cancer cells..Nature2012;483:570-5 PMCID:PMC3349233

[7]

Klijn C,Stawiski EW,Jiang Z.A comprehensive transcriptional portrait of human cancer cell lines..Nat Biotechnol2015;33:306-12

[8]

Campbell J,Brough R,Pemberton HN.Large-scale profiling of kinase dependencies in cancer cell lines..Cell Rep2016; 15;14:2490-501 PMCID:PMC4802229

[9]

Polyak K,Campbell IG.Co-evolution of tumor cells and their microenvironment..Trends Genet2008;25:30-8

[10]

McGranahan N.Biological and therapeutic impact of intratumor heterogeneity in cancer evolution..Cancer Cell2015;27:15-26

[11]

Belizario JE,Perez-Sosa M,Moreira DF.Using pharmacogenomic databases for discovering patient-target genes and small molecule candidates to cancer therapy..Front Pharmacol2016;7:312 PMCID:PMC5040751

[12]

Feinberg AP,Göndör A.Epigenetic modulators, modifiers and mediators in cancer aetiology and progression..Nat Rev Genet2016;17:284-99 PMCID:PMC4888057

[13]

Roy DM,Chan TA.Driver mutations of cancer epigenomes..Protein Cell2014;5:265-96 PMCID:PMC3978161

[14]

Jeggo PA,Carr AM.DNA repair, genome stability and cancer: A historical perspective..Nat Rev Cancer2016;16:35-42

[15]

Stirzaker C,Statham AL.Mining cancer methylomes: prospects and challenges..Trends Genet2014;30:75-84

[16]

Yao L,Laird PW,Berman BP.Inferring regulatory element landscapes and transcription factor networks from cancer methylomes..Genome Biol.2015;16:105 PMCID:PMC4460959

[17]

Widschwendter M,Evans I,Dillner J.Epigenome-based cancer risk prediction: rationale, opportunities and challenges..Nat Rev Clin Oncol2018;15:292-309

[18]

Mahoney KM,Freeman GJ.Combination cancer immunotherapy and new immunomodulatory targets..Nat Rev Drug Discov2015;14:561-84

[19]

Blank CU,Ribas A.Cancer Immunology. The cancer Immunogram..Science2016;352:658-60

[20]

Dumont N,DeFilippis RA,Rabban JT.Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics..Neoplasia2013;15:249 PMCID:PMC3593149

[21]

Thorsson V,Brown SD,Bortone DS.The immune landscape of cancer..Immunity2018;48:812-30 PMCID:PMC5982584

[22]

Wang JC.Cancer stem cells: lessons from leukemia..Trends Cell Biol2005;15:494-501

[23]

Park SY,Li H,Gelman R.Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer..Clin Cancer Res2010;16:876-87 PMCID:PMC2818503

[24]

Kalluri R.The basics of epithelial-mesenchymal transition..J Clin Invest2009;119:1420-8 PMCID:PMC2689101

[25]

Aparicio S.Tumor heterogeneity: next-generation sequencing enhances the view from pathologist’s microscope..Genome Biol2014;15:463 PMCID:PMC4318188

[26]

Laskin J,Aparicio S,Ch’ng C.Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers..Cold Spring Harb Mol Case Stud2015;1:a000570 PMCID:PMC4850882

[27]

Mertins P,Ruggles KV,Clauser KR.Proteogenomics connects somatic mutations to signaling in breast cancer..Nature2016;534:55-62 PMCID:PMC5102256

[28]

Guerin M,Toiron Y,Audebert S.How may targeted proteomics complement genomic data in breast cancer?.Expert Rev Proteomics2017;14:43-54

[29]

Shipitsin M,Argani P,Bloushtain-Qimron N.Molecular definition of breast tumor heterogeneity..Cancer Cell2007;11:259-73

[30]

Reis-Filho J.Gene expression profiling in breast cancer: classification, prognostication, and prediction..Lancet2011;378:1812-23

[31]

Gudjonsson T,Sternlicht MD,Bissel MJ.Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia..J Mammary Gland Biol Neoplasia2005;10:261-72 PMCID:PMC2798159

[32]

Stephens PJ,Davies H,Greenman C.The landscape of cancer genes and mutational processes in breast cancer..Nature2012;486:400-4 PMCID:PMC3428862

[33]

Sorlie T,Parker J,Marron JS.Repeated observation of breast tumor subtypes in independent gene expression data sets..Proc Natl Acad Sci U S A2003;100:8418-23 PMCID:PMC166244

[34]

Curtis CSP,Chin G,Rueda MJ.The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups..Nature2012;486:346-52 PMCID:PMC3440846

[35]

Perou CM,Eisen MB,Jeffrey SS.Molecular portraits of human breast tumours..Nature2000;406:747-52

[36]

De Mattos-Arruda L,Piscuoglio S,Lim RS.Genetic heterogeneity and actionable mutations in HER2-positive primary breast cancers and their brain metastases..Oncotarget2018;9:20617-30 PMCID:PMC5945519

[37]

Turner NC.Basal-like breast cancer and the BRCA1 phenotype..Oncogene2006;25:5846-53

[38]

Gonzalez-Angulo AM,Hortobagyi GN.Overview of resistance to systemic therapy in patients with breast cancer..Adv Exp Med Biol2007;608:1-22

[39]

Razavi P,Xu G,Ross DS.The genomic landscape of endocrine-resistant advanced breast cancers..Cancer Cell2018;34:427-38 PMCID:PMC6327853

[40]

Arteaga CL,Osborne CK,Puglisi F.Treatment of HER2-positive breast cancer: current status and future perspectives..Nat Rev Clin Oncol2012;9:16-32

[41]

Pareja F.Triple-negative breast cancers - a panoply of cancer types..Nat Rev Clin Oncol2018;15:347-8

[42]

Cancer Genome Atlas NetworkComprehensive molecular portraits of human breast tumours..Nature2012;490:61-70 PMCID:PMC3465532

[43]

Alexandrov LB,Wedge DC,Behjati S.Signatures of mutational processes in human cancer..Nature2013;500:415-21 PMCID:PMC3776390

[44]

Mundim FG,Nonogaki S,Soares FA.Breast carcinoma-associated fibroblasts share similar biomarker profiles in matched lymph node metastasis..Appl Immunohistochem Mol Morphol2016;24:712-20

[45]

Harris LN,McShane LM,Collyar DE.Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage Invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline..J Clin Oncol2016;34:1134-50 PMCID:PMC4933134

[46]

Weaver DL,Krag DN,Anderson SJ.Effect of occult metastases on survival in node-negative breast cancer..N Engl J Med2011;364:412-21 PMCID:PMC3044504

[47]

Liu MC,Mardis ER,Friedman PN.PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)..NPJ Breast Cancer2016;2:15023 PMCID:PMC5501351

[48]

Li WX,Tang L,Li GH.Comprehensive tissue-specific gene set enrichment analysis and transcription factor analysis of breast cancer by integrating 14 gene expression datasets..Oncotarget2017;8:6775-86 PMCID:PMC5351668

[49]

Bancovik J,Porter D,Yao J.Dermcidin exerts its oncogenic effects in breast cancer via modulation ERBB signaling..BMC Cancer2015;15:70 PMCID:PMC4353460

[50]

Wilhelm M,Hahne H,Lieberenz M.Mass-spectrometry-based draft of the human proteome..Nature2014;509:582-7

[51]

Scaltriti M,Bradbury I,Agbor-Tarh D.High HER2 expression correlates with response to the combination of lapatinib and trastuzumab..J. Clin Cancer Res2015;21:569-76

[52]

Kirouac DC,Lahdenranta J,Nielsen UB.HER2+ cancer cell dependence on PI3K vs. MAPK signaling axes is determined by expression of EGFR, ERBB3 and CDKN1B..PLoS Comput Biol2016;12:e1004827 PMCID:PMC4818107

[53]

Osmanbeyoglu HU,Bromberg JF.Linking signaling pathways to transcriptional programs in breast cancer..Genome Res2014;24:1869-80 PMCID:PMC4216927

[54]

Osmanbeyoglu HU,Chan C,Leslie CS.Pancancer modelling predicts the context-specific impact of somatic mutations on transcriptional programs..Nature Commun2017;8:14249 PMCID:PMC5290314

[55]

Fackler MJ,Williams D,Cruz LA.Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence..Cancer Res2011;71:6195-207 PMCID:PMC3308629

[56]

Su Y,Bloushtain-Qimron N,Krzystanek M.Somatic cell fusions reveal extensive heterogeneity in basal-like breast cancer..Cell Rep2015;11:1549-63

[57]

Droog M,Zwart W.The estrogen receptor α-cistrome beyond breast cancer..Mol Endocrinol2016;30:1046-58 PMCID:PMC5414603

[58]

Mei S,Zheng R,Wu Q.Cistrome Cancer: a web resource for integrative gene regulation modeling in cancer..Cancer Res2017;77:19-22 PMCID:PMC5826647

[59]

Fleischer T,Mathelier A,Nebdal D.DNA methylation at enhancers identifies distinct breast cancer lineages..Nat Commun2017;8:1379 PMCID:PMC5680222

[60]

Garrido-Castro AC.CDK4/6 Inhibition in breast cancer: mechanisms of response and treatment failure..Curr Breast Cancer Rep2017;9:26-33 PMCID:PMC5414585

[61]

Goel S,Watt AC,Sceneay J.CDK4/6 inhibition triggers anti-tumour immunity..Nature2017;548:471-5 PMCID:PMC5570667

[62]

Fiegl H,Goebel G,Marth C.Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer..Cancer Res2006;66:29-33

[63]

Costa A,Scholer-Dahirel A,Bourachot B.Fibroblast heterogeneity and immunosuppressive environment in human breast cancer..Cancer Cell2018;33:463-79

[64]

Force J,McArthur HL.Checkpoint blockade strategies in the treatment of breast cancer: where we are and where we are heading..Curr Treat Options Oncol2019;20:35

[65]

Mori H,Yamaguchi R,Osako T.The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer..Oncotarget2017;8:15584-92 PMCID:PMC5362507

[66]

Yeong J,Lee B,Ong CCH.Prognostic value of CD8+ PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer..J Immunother Cancer2019;7:34 PMCID:PMC6366051

[67]

Dzutsev A,Perez-Chanona E,Salcedo R.Microbes and cancer..Annu Rev Immunol2017;35:199-228

[68]

Thompson KJ,Tang X,Jeraldo PR.A comprehensive analysis of breast cancer microbiota and host gene expression..PLoS One2017;12:e0188873 PMCID:PMC5708741

[69]

Routy B,Derosa L,Alou MT.Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors..Science2018;359:91-7

[70]

D’Abreo N.Immune-checkpoint inhibition for metastatic triple-negative breast cancer: safety first?.Nat Rev Clin Oncol2019;16:399-400

[71]

Rojas K.Breast cancer epidemiology and risk factors..Clin Obstet Gynecol2016;59:651-72

[72]

Safe S.Endocrine disruption: relevance of experimental studies in female animals to human studies..Curr Opin Toxicol2017;3:12-9

[73]

Reid G.Can breast microbiota provide protective effects against cancer?.Future Microbiol2016;11:987-99

[74]

Hamada T,Nishihara R.Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis..J Gastroenterol2017;52:265-75 PMCID:PMC5325774

[75]

Ogino S,Hamada T,Nishihara R.Insights into pathogenic interactions among environment, host, and tumor at the crossroads of molecular pathology and epidemiology..Annu Rev Pathol2019;14:83-103 PMCID:PMC6345592

AI Summary AI Mindmap
PDF

183

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/