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• W3182636721 abstract "Triple-negative breast cancer (TNBC), which is the most malignant subtype of breast cancer (BC), accounts for 10%–20% of all BC cases. TNBC, which occurs more frequently in young women, is characterized by high rates of cell proliferation and metastasis and poor prognosis. Chemotherapy is the primary systemic therapeutic strategy for TNBC. However, chemotherapy is largely unsuccessful, and effective targeted therapies for TNBC have not been established. Therefore, it is a matter of great urgency to identify precise molecular targets for the promising prognosis of patients with TNBC. Circular RNAs (circRNAs), which are a type of non-coding RNAs (ncRNAs), are abundantly expressed in the eukaryotic cells and exhibit diverse cellular functions. The roles of circRNAs are to sponge microRNA or RNA-binding proteins, regulate gene expression, and serve as templates for translation. Here, we review the current findings on the potential of circRNAs as a diagnostic, prognostic, and therapeutic biomarker for TNBC. However, further studies are essential to elucidate the functions of circRNAs in TNBC. This review also discusses the current limitations and future directions of TNBC-associated circRNAs, which can facilitate the translation of experimental research into clinical application. Triple-negative breast cancer (TNBC), which is the most malignant subtype of breast cancer (BC), accounts for 10%–20% of all BC cases. TNBC, which occurs more frequently in young women, is characterized by high rates of cell proliferation and metastasis and poor prognosis. Chemotherapy is the primary systemic therapeutic strategy for TNBC. However, chemotherapy is largely unsuccessful, and effective targeted therapies for TNBC have not been established. Therefore, it is a matter of great urgency to identify precise molecular targets for the promising prognosis of patients with TNBC. Circular RNAs (circRNAs), which are a type of non-coding RNAs (ncRNAs), are abundantly expressed in the eukaryotic cells and exhibit diverse cellular functions. The roles of circRNAs are to sponge microRNA or RNA-binding proteins, regulate gene expression, and serve as templates for translation. Here, we review the current findings on the potential of circRNAs as a diagnostic, prognostic, and therapeutic biomarker for TNBC. However, further studies are essential to elucidate the functions of circRNAs in TNBC. This review also discusses the current limitations and future directions of TNBC-associated circRNAs, which can facilitate the translation of experimental research into clinical application. Breast cancer (BC) is a threat to human health, as it is associated with a high mortality rate. According to the American Cancer Society report of 2019, 271,000 new BC cases and 42,260 BC-related deaths were reported in the United States.1Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2019.CA Cancer J. Clin. 2019; 69: 7-34Crossref PubMed Scopus (10926) Google Scholar Among the BC subtypes, triple-negative breast cancer (TNBC) is associated with poor overall survival (OS) and disease-free survival (DFS).2Onitilo A.A. Engel J.M. Greenlee R.T. Mukesh B.N. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival.Clin. Med. Res. 2009; 7: 4-13Crossref PubMed Google Scholar TNBC, which accounts for 10%–20% of all BC cases, does not exhibit the expression of hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]) and human epidermal growth factor receptor 2 (HER2).3Dent R. Trudeau M. Pritchard K.I. Hanna W.M. Kahn H.K. Sawka C.A. Lickley L.A. Rawlinson E. Sun P. Narod S.A. Triple-negative breast cancer: clinical features and patterns of recurrence.Clin. Cancer Res. 2007; 13: 4429-4434Crossref PubMed Scopus (2866) Google Scholar,4Venkitaraman R. Triple-negative/basal-like breast cancer: clinical, pathologic and molecular features.Expert Rev. Anticancer Ther. 2010; 10: 199-207Crossref PubMed Google Scholar Lehmann et al.5Lehmann B.D. Jovanović B. Chen X. Estrada M.V. Johnson K.N. Shyr Y. Moses H.L. Sanders M.E. Pietenpol J.A. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.PLoS ONE. 2016; 11: e0157368Crossref PubMed Google Scholar defined TNBC molecular subtypes into four tumor-specific subtypes: basal-like 1 (BL1) and 2 (BL2), mesenchymal (M), and one luminal androgen receptor group (LAR). The phenotypes of TNBC, which is frequent among young patients, include large size and advanced tumor grade.3Dent R. Trudeau M. Pritchard K.I. Hanna W.M. Kahn H.K. Sawka C.A. Lickley L.A. Rawlinson E. Sun P. Narod S.A. Triple-negative breast cancer: clinical features and patterns of recurrence.Clin. Cancer Res. 2007; 13: 4429-4434Crossref PubMed Scopus (2866) Google Scholar,6Carey L. Winer E. Viale G. Cameron D. Gianni L. Triple-negative breast cancer: disease entity or title of convenience?.Nat. Rev. Clin. Oncol. 2010; 7: 683-692Crossref PubMed Scopus (561) Google Scholar,7Yin W.-J. Lu J.-S. Di G.-H. Lin Y.-P. Zhou L.-H. Liu G.-Y. Wu J. Shen K.-W. Han Q.-X. Shen Z.-Z. Shao Z.-M. Clinicopathological features of the triple-negative tumors in Chinese breast cancer patients.Breast Cancer Res. Treat. 2009; 115: 325-333Crossref PubMed Scopus (90) Google Scholar Patients with TNBC exhibit poor survival rates owing to the metastatic properties of the tumor. TNBCs would have metastasized to local and distant lymph nodes at diagnosis and exhibit high proliferative rates, which may be attributed to genetic and molecular aberrations.6Carey L. Winer E. Viale G. Cameron D. Gianni L. Triple-negative breast cancer: disease entity or title of convenience?.Nat. Rev. Clin. Oncol. 2010; 7: 683-692Crossref PubMed Scopus (561) Google Scholar,8Shah S.P. Roth A. Goya R. Oloumi A. Ha G. Zhao Y. Turashvili G. Ding J. Tse K. Haffari G. et al.The clonal and mutational evolution spectrum of primary triple-negative breast cancers.Nature. 2012; 486: 395-399Crossref PubMed Scopus (1361) Google Scholar, 9Pal S.K. Childs B.H. Pegram M. Triple negative breast cancer: unmet medical needs.Breast Cancer Res. Treat. 2011; 125: 627-636Crossref PubMed Scopus (223) Google Scholar, 10Koboldt D.C. Fulton R.S. McLellan M.D. Schmidt H. Kalicki-Veizer J. McMichael J.F. Fulton L.L. Dooling D.J. Ding L. Mardis E.R. et al.Cancer Genome Atlas NetworkComprehensive molecular portraits of human breast tumours.Nature. 2012; 490: 61-70Crossref PubMed Scopus (7326) Google Scholar Women with TNBC, especially African American women, exhibit high rates of early distant recurrence and a poor 5-year prognosis.6Carey L. Winer E. Viale G. Cameron D. Gianni L. Triple-negative breast cancer: disease entity or title of convenience?.Nat. Rev. Clin. Oncol. 2010; 7: 683-692Crossref PubMed Scopus (561) Google Scholar The carcinogenesis of TNBC is a complex process that involves genetic mutations and dysregulation of epigenetic pathways. Previous studies have examined the epigenetic changes (such as DNA methylation11Pinto R. De Summa S. Pilato B. Tommasi S. DNA methylation and miRNAs regulation in hereditary breast cancer: epigenetic changes, players in transcriptional and post- transcriptional regulation in hereditary breast cancer.Curr. Mol. Med. 2014; 14: 45-57Crossref PubMed Scopus (14) Google Scholar,12Gao Y. Jones A. Fasching P.A. Ruebner M. Beckmann M.W. Widschwendter M. Teschendorff A.E. The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.Clin. Epigenetics. 2015; 7: 126Crossref PubMed Google Scholar), non-coding RNA (ncRNA) profile,13Huarte M. Guttman M. Feldser D. Garber M. Koziol M.J. Kenzelmann-Broz D. Khalil A.M. Zuk O. Amit I. Rabani M. et al.A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.Cell. 2010; 142: 409-419Abstract Full Text Full Text PDF PubMed Scopus (1564) Google Scholar,14Koduru S.V. Tiwari A.K. Leberfinger A. Hazard S.W. Kawasawa Y.I. Mahajan M. Ravnic D.J. A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer.J. Cancer. 2017; 8: 578-596Crossref PubMed Scopus (15) Google Scholar and somatic mutation profile in TNBC.15Anders C.K. Carey L.A. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer.Clin. Breast Cancer. 2009; 9: S73-S81Abstract Full Text PDF PubMed Scopus (414) Google Scholar,16Anders C. Carey L.A. Understanding and treating triple-negative breast cancer.Oncology (Williston Park). 2008; 22: 1233-1239, discussion 1239–1240, 1243PubMed Google Scholar ncRNA LOC339535 (commonly referred to as LINK-A), which is involved in the carcinogenesis of TNBC, is associated with poor prognosis and progression-free survival in patients with TNBC.17Lin A. Li C. Xing Z. Hu Q. Liang K. Han L. Wang C. Hawke D.H. Wang S. Zhang Y. Wei Y. et al.The LINK-A lncRNA activates normoxic HIF1 alpha signalling in triple-negative breast cancer.Nat. Cell Biol. 2016; 18: 213-224Crossref PubMed Scopus (0) Google Scholar Additionally, the dysregulation of various ncRNAs, including microRNAs and long-ncRNAs (lncRNAs), contributes to tumorigenesis and tumor progression.13Huarte M. Guttman M. Feldser D. Garber M. Koziol M.J. Kenzelmann-Broz D. Khalil A.M. Zuk O. Amit I. Rabani M. et al.A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.Cell. 2010; 142: 409-419Abstract Full Text Full Text PDF PubMed Scopus (1564) Google Scholar,14Koduru S.V. Tiwari A.K. Leberfinger A. Hazard S.W. Kawasawa Y.I. Mahajan M. Ravnic D.J. A Comprehensive NGS Data Analysis of Differentially Regulated miRNAs, piRNAs, lncRNAs and sn/snoRNAs in Triple Negative Breast Cancer.J. Cancer. 2017; 8: 578-596Crossref PubMed Scopus (15) Google Scholar Thus, the therapeutic potential of targeting ncRNAs has piqued the interest of the scientific community. Currently, the standard treatment for patients with TNBC is the application of chemotherapeutic agents, such as anthracyclines, alkylating agents, taxanes, or platinum salts.18Bianchini G. Balko J.M. Mayer I.A. Sanders M.E. Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.Nat. Rev. Clin. Oncol. 2016; 13: 674-690Crossref PubMed Scopus (1015) Google Scholar,19Foulkes W.D. Smith I.E. Reis-Filho J.S. Triple-negative breast cancer.N. Engl. J. Med. 2010; 363: 1938-1948Crossref PubMed Scopus (2291) Google Scholar Poly(ADP-ribose) polymerase (PARP) inhibitors have been approved for the treatment of BRCA mutant TNBC.20Robson M. Im S.A. Senkus E. Xu B. Domchek S.M. Masuda N. Delaloge S. Li W. Tung N. Armstrong A. et al.Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.N. Engl. J. Med. 2017; 377: 523-533Crossref PubMed Scopus (1191) Google Scholar Additionally, immune modulators are promising therapeutics for TNBC.21Schmid P. Adams S. Rugo H.S. Schneeweiss A. Barrios C.H. Iwata H. Diéras V. Hegg R. Im S.A. Shaw Wright G. et al.IMpassion130 Trial InvestigatorsAtezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.N. Engl. J. Med. 2018; 379: 2108-2121Crossref PubMed Scopus (1586) Google Scholar The combination of nab-paclitaxel and atezolizumab (anti-PD-L1) was recently approved by the US Food and Drug Administration (FDA) for the patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 based on a PFS benefit over chemotherapy in the Impassion130 trial.22Murciano-Goroff Y.R. Warner A.B. Wolchok J.D. The future of cancer immunotherapy: microenvironment-targeting combinations.Cell Res. 2020; 30: 507-519Crossref PubMed Scopus (136) Google Scholar However, further studies are needed to develop effective targeted therapeutics for TNBC. Recent studies have reported that chemotherapy is associated with unsatisfactory clinical outcomes in patients with TNBC.18Bianchini G. Balko J.M. Mayer I.A. Sanders M.E. Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.Nat. Rev. Clin. Oncol. 2016; 13: 674-690Crossref PubMed Scopus (1015) Google Scholar Hence, there is a need to identify novel biomarkers, as well as novel genetic and epigenetic therapeutic targets, for TNBC. The identification of ncRNAs has increased our understanding of the pathogenesis of TNBC and can aid in the development of novel therapeutic strategies for TNBC. More than 80% of cancer-associated single-nucleotide polymorphisms are reported in non-coding regions of the genome. Thus, ncRNAs, which contribute to TNBC carcinogenesis, can be a potential therapeutic target for TNBC.23Cheetham S.W. Gruhl F. Mattick J.S. Dinger M.E. Long noncoding RNAs and the genetics of cancer.Br. J. Cancer. 2013; 108: 2419-2425Crossref PubMed Scopus (593) Google Scholar Circular RNAs (circRNAs), a subclass of ncRNAs abundantly expressed in the eukaryotic cells, are covalent single-chain closed-loop structures that lack terminal 5¢ and 3¢ ends.24Patop I.L. Wüst S. Kadener S. Past, present, and future of circRNAs.EMBO J. 2019; 38: e100836Crossref PubMed Scopus (268) Google Scholar Sanger et al.25Sanger H.L. Klotz G. Riesner D. Gross H.J. Kleinschmidt A.K. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures.Proc. Natl. Acad. Sci. USA. 1976; 73: 3852-3856Crossref PubMed Scopus (1087) Google Scholar first discovered circRNAs in 1976. The functions of circRNAs were recently elucidated after the development of sequencing techniques.24Patop I.L. Wüst S. Kadener S. Past, present, and future of circRNAs.EMBO J. 2019; 38: e100836Crossref PubMed Scopus (268) Google Scholar Structural characteristics of circRNAs have a decisive effect on their own performances, which means that they have obvious advantages as biomarkers of clinical diseases on account of the high stability and evolutionary conservation.26Vo J.N. Cieslik M. Zhang Y. Shukla S. Xiao L. Zhang Y. Wu Y.M. Dhanasekaran S.M. Engelke C.G. Cao X. et al.The Landscape of Circular RNA in Cancer.Cell. 2019; 176: 869-881.e13Abstract Full Text Full Text PDF PubMed Scopus (511) Google Scholar Hence, further studies are needed to elucidate the role of circRNAs in the regulation of various pathological conditions.27Arnaiz E. Sole C. Manterola L. Iparraguirre L. Otaegui D. Lawrie C.H. CircRNAs and cancer: Biomarkers and master regulators.Semin. Cancer Biol. 2019; 58: 90-99Crossref PubMed Scopus (139) Google Scholar Recently, the regulatory function of circRNAs has been demonstrated in several solid tumors, such as colorectal cancer (CRC) or prostate cancer.28Patop I.L. Kadener S. circRNAs in Cancer.Curr. Opin. Genet. Dev. 2018; 48: 121-127Crossref PubMed Scopus (209) Google Scholar, 29Hua J.T. Chen S. He H.H. Landscape of Noncoding RNA in Prostate Cancer.Trends Genet. 2019; 35: 840-851Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 30Zhang M. Xin Y. Circular RNAs: a new frontier for cancer diagnosis and therapy.J. Hematol. Oncol. 2018; 11: 21Crossref PubMed Scopus (105) Google Scholar Additionally, circRNAs are involved in TNBC cell proliferation, apoptosis, migration, and invasion. This review summarizes the role of circRNAs in TNBC and the potential underlying molecular mechanisms to aid therapeutic applications. A comprehensive understanding of circRNAs may provide useful information for the clinical application of circRNA-based biomarkers. Chemotherapy is the primary systemic treatment for both early-stage and advanced TNBC, a pathological condition for which molecular targeted therapy has not been developed.18Bianchini G. Balko J.M. Mayer I.A. Sanders M.E. Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.Nat. Rev. Clin. Oncol. 2016; 13: 674-690Crossref PubMed Scopus (1015) Google Scholar,31Coates A.S. Winer E.P. Goldhirsch A. Gelber R.D. Gnant M. Piccart-Gebhart M. Thürlimann B. Senn H.J. Panel MembersTailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.Ann. Oncol. 2015; 26: 1533-1546Abstract Full Text Full Text PDF PubMed Scopus (1136) Google Scholar Although TNBC is associated with a high metastatic rate (30%–40%),32Haffty B.G. Yang Q. Reiss M. Kearney T. Higgins S.A. Weidhaas J. Harris L. Hait W. Toppmeyer D. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer.J. Clin. Oncol. 2006; 24: 5652-5657Crossref PubMed Scopus (843) Google Scholar neoadjuvant chemotherapy (NAC) and standard surgery are the most effective approaches to improve OS of patients with early-stage TNBC.33Golshan M. Cirrincione C.T. Sikov W.M. Berry D.A. Jasinski S. Weisberg T.F. Somlo G. Hudis C. Winer E. Ollila D.W. Alliance for Clinical Trials in OncologyImpact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).Ann. Surg. 2015; 262: 434-439, discussion 438–439Crossref PubMed Scopus (94) Google Scholar,34von Minckwitz G. Untch M. Blohmer J.-U. Costa S.D. Eidtmann H. Fasching P.A. Gerber B. Eiermann W. Hilfrich J. Huober J. et al.Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.J. Clin. Oncol. 2012; 30: 1796-1804Crossref PubMed Scopus (1486) Google Scholar Interestingly, even with what is deemed as a poor OS, subsets of patients with TNBC have a better response to chemotherapy than those with other subtypes. It is the so-called TNBC paradox, because patients with TNBC are associated with a high risk of recurrence but also benefit from treatment.35Carey L.A. Dees E.C. Sawyer L. Gatti L. Moore D.T. Collichio F. Ollila D.W. Sartor C.I. Graham M.L. Perou C.M. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes.Clin. Cancer Res. 2007; 13: 2329-2334Crossref PubMed Scopus (1514) Google Scholar Disease recurrence in patients with TNBC can be attributed to the residual tumor cells that are not killed after NAC.32Haffty B.G. Yang Q. Reiss M. Kearney T. Higgins S.A. Weidhaas J. Harris L. Hait W. Toppmeyer D. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer.J. Clin. Oncol. 2006; 24: 5652-5657Crossref PubMed Scopus (843) Google Scholar A recent study36Farmer H. McCabe N. Lord C.J. Tutt A.N.J. Johnson D.A. Richardson T.B. Santarosa M. Dillon K.J. Hickson I. Knights C. et al.Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature. 2005; 434: 917-921Crossref PubMed Scopus (4153) Google Scholar reported that the efficacy of NAC can be enhanced with the use of dose-dense and high-dose regimens in TNBC. Taxanes and anthracyclines are the major therapeutics used in NAC.37Henderson I.C. Berry D.A. Demetri G.D. Cirrincione C.T. Goldstein L.J. Martino S. Ingle J.N. Cooper M.R. Hayes D.F. Tkaczuk K.H. et al.Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer.J. Clin. Oncol. 2003; 21: 976-983Crossref PubMed Scopus (1114) Google Scholar,38Nash I. HER2 and response to paclitaxel in node-positive breast cancer.N. Engl. J. Med. 2008; 358: 198-author reply 198–199PubMed Google Scholar Additionally, the correlation of NAC, which is associated with toxicity, with improved pathological complete response rate and event-free survival has not been established. Hence, the application of platinum-based agents to standard NAC has been disputed in clinical practice.18Bianchini G. Balko J.M. Mayer I.A. Sanders M.E. Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.Nat. Rev. Clin. Oncol. 2016; 13: 674-690Crossref PubMed Scopus (1015) Google Scholar The 5-year survival rate in women with metastatic BC is less than 30%, and almost all patients with metastatic TNBC will ultimately die of the disease.39Bonotto M. Gerratana L. Poletto E. Driol P. Giangreco M. Russo S. Minisini A.M. Andreetta C. Mansutti M. Pisa F.E. et al.Measures of outcome in metastatic breast cancer: insights from a real-world scenario.Oncologist. 2014; 19: 608-615Crossref PubMed Scopus (124) Google Scholar The European Society for Medical Oncology (ESMO)40Cardoso F. Costa A. Norton L. Senkus E. Aapro M. André F. Barrios C.H. Bergh J. Biganzoli L. Blackwell K.L. et al.European School of OncologyEuropean Society of Medical OncologyESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2).Breast. 2014; 23: 489-502Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar and American Society of Clinical Oncology (ASCO)41Partridge A.H. Rumble R.B. Carey L.A. Come S.E. Davidson N.E. Di Leo A. Gralow J. Hortobagyi G.N. Moy B. Yee D. et al.Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline.J. Clin. Oncol. 2014; 32: 3307-3329Crossref PubMed Scopus (188) Google Scholar recommend sequential single-component chemotherapy for patients with metastatic tumors unless the progression of the disease or visceral crisis is rapid. The efficacy of single-component therapeutic agents against metastatic tumors is lower than that of combination therapies. However, combination therapy is associated with high cost and increased toxicity and provides limited survival benefits.42Conlin A.K. Seidman A.D. Taxanes in breast cancer: an update.Curr. Oncol. Rep. 2007; 9: 22-30Crossref PubMed Scopus (36) Google Scholar Based on the results of clinical or preclinical trials (Table 1), various molecular targets have been proposed to improve the prognosis of TNBC and overcome the intrinsic resistance to chemotherapy. The clinical trials of therapeutic agents, such as PARP inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, MEK inhibitors, and histone deacetylase (HDAC) inhibitors targeting various signaling pathways,43Balko J.M. Giltnane J.M. Wang K. Schwarz L.J. Young C.D. Cook R.S. Owens P. Sanders M.E. Kuba M.G. Sánchez V. et al.Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets.Cancer Discov. 2014; 4: 232-245Crossref PubMed Scopus (277) Google Scholar have yielded beneficial clinical outcomes in approximately 90% of TNBC cases.Table 1Progressive clinical trials on TNBC target therapy in the search of therapeutic biomarkersClinical trialPhaseInterventionsIndicationsTherapeutic targetNCT02163694IIIexperimental group: veliparib (o.a.), days 2 to 5 of a 21-day cycle; carboplatin (i.v.), day 1 of a 21-day cycle; paclitaxel (Taxol) (i.v.), days 1, 8, and 15 of a 21-day cycle; control group: placebo (o.a.), days 2 to 5 of a 21-day cycle; carboplatin (i.v.), day 1 of a 21-day cycle; paclitaxel (Taxol) (i.v.), days 1, 8, and 15 of a 21-day cyclemetastatic TNBCPARP inhibitorNCT02000622IIIgroup 1: olaparib (300 mg; o.a.), twice daily at 12-h intervals; group 2: capecitabine (Xeloda) (2,500 mg/m2; i.v.), days 1–14, q21; vinorelbine (30 mg/m2; o.a.), days 1,8, and q21; or eribulin (1.4 mg/m2; i.v.), days 1, 8, and q21metastatic breast cancerPARP inhibitorNCT02032823IIIgroup 1: olaparib (300 mg; o.a.), twice daily at 12-h intervals; group 2: placebo (300 mg; o.a.), twice daily at 12-h intervalsearly-stage TNBCPARP inhibitorNCT01945775IIIexperimental group: talazoparib (1.0 mg; o.a.), once daily for 21 continuous days; control group: capecitabine, eribulin, gemcitabine, or vinorelbine (o.a.), once daily for 21 continuous daysPARP inhibitorNCT01623349Igroup 1: olaparib (starting dose 50 mg; o.a.), twice daily; BKM120 (starting dose 40 mg; o.a.), once daily; group 2: olaparib (starting dose 100 mg; o.a.), twice daily; BYL719 (starting dose 250 mg; o.a.), once dailyrecurrent TNBCPI3K inhibitorNCT02000882IIBKM120 (o.a.), daily; capecitabine (o.a.), twice a day for 2 weeks on/1 week off, ongoingTNBC with brain metastasesPI3K inhibitorNCT03243838I–IIfour cycles of docetaxel and apatinib combination, followed by four cycles of epirubicin and cyclophosphamide combinationearly-stage TNBCsmall inhibitor of EGFRNCT02623972IIeribulin (Halaven) (i.v.) for four cycles, followed by AC (i.v.) for four cyclesadvanced TNBCinhibitor of microtubule dynamicsNCT02120469Ieverolimus (Afinitor) (o.a.), daily; eribulin mesylate (Halaven) (i.v.) twice every monthmetastatic TNBCmTOR inhibitorNCT02672475Ipaclitaxel (Taxol) (i.v.), weekly with 3 weeks on/1 week off; galunisertib (LY2157299) (o.a.), twice daily with 3 weeks on/1 week offmetastatic TNBCinhibitor of the TGF-β receptor I kinaseNCT02632071IACY-1215 (ricolinostat) (o.a.), daily with 3 weeks on/1 week off; nab-paclitaxel (Abraxane) (i.v.), weekly with 3 weeks on/1 week offadvanced TNBCHDAC6 blockerNCT02393794I–IIromidepsin (Istodax) (i.v.), twice every 3 weeks; cisplatin (Platinol), (i.v.), every 3 weeksTNBCHDAC inhibitorNCT02425891IIIexperimental group: MPDL3280a (atezolizumab) (i.v.); nab-paclitaxel (Abraxane) (i.v.); control group: placebo; nab-paclitaxel (Abraxane) (i.v.)locally advanced or metastatic TNBCanti-PD-L1NCT02309177Igroup 1: nab-paclitaxel (i.v.), weekly for 3 weeks every month; nivolumab (Opdivo) (i.v.), every 2 weeks starting at 3 months; group 2: nab-paclitaxel (i.v.), once every 3 weeks; nivolumab (Opdivo) (i.v.), every 3 weeks starting at 3 monthsrecurrent metastatic TNBCanti-PD-1NCT02366949Iexperimental group: BAY1217389 (o.a.), twice daily; paclitaxel (Taxol) (i.v.), weekly; control group: paclitaxel (Taxol) (i.v.), weeklyadvanced TNBCMPS1NCT02595320IIgroup 1: capecitabine (Xeloda) (1,500 mg; o.a.), twice daily with 1 week on/1 week off; group 2: capecitabine (Xeloda) (1,250 mg; o.a.), twice daily with 2 weeks on/1 week offmetastatic TNBCalkylating agent; tumor-selective and tumor-activated cytotoxic agentNCT02929576IIIgroup 1: Xtandi and Taxol, enzalutamide (Xtandi) (o.a.), daily, ongoing; paclitaxel (Taxol) (i.v.), weekly for 16 weeks; group 2: placebo (o.a.), daily, ongoing; paclitaxel (Taxol) (i.v.), weekly for 16 weeks; group 3: Xtandi followed by Taxol, enzalutamide (Xtandi) (o.a.), daily, ongoing; paclitaxel (Taxol) (i.v.), weekly for 16 weeksadvanced TNBCsynthetic non-steroidal antiandrogenNCT02187991IIgroup 1: paclitaxel (Taxol) (i.v.), 3 times a month, ongoing; group 2: paclitaxel (Taxol) (i.v.), 3 times a month, ongoing; alisertib (o.a.), 3 times a week, ongoingadvanced TNBCaurora A kinase inhibitorNCT02950064IBTP-114 (i.v.), once every 3 weeks, ongoingadvanced TNBCalbumin-binding cisplatin prodrugNCT02624700IIpemetrexed (i.v.), every 2 weeks; sorafenib (o.a.), twice daily for 5 daysrecurrent or metastatic TNBCsmall inhibitor of several tyrosine protein kinases, such as VEGFR, PDGFR, and Raf family kinases (more avidly C-Raf than B-Raf)NCT02978716IIgroup 1 (chemotherapy only): gemcitabine (Gemzar) and carboplatin (Paraplatin) (i.v.) on days 1 and 8, ongoing; group 2 (trilaciclib and chemotherapy): trilaciclib (G1T28) (i.v.) on days 1 and 8, ongoing; gemcitabine (Gemzar) and carboplatin (Paraplatin) (i.v.) on days 1 and 8, ongoing; group 3 (trilaciclib and chemotherapy): trilaciclib (G1T28) (i.v.) on days 1, 2, 8, and 9, ongoing; gemcitabine (Gemzar) and carboplatin (Paraplatin) (i.v.) on days 2 and 9, ongoingrecurrent or metastatic TNBCCDK4/6 inhibitori.v., intravenous; o.a., oral administration; mTOR, mammalian target of rapamycin; HDAC6, histone deacetylase 6; PD-L1, programmed cell death ligand 1; MPS1, serine/threonine kinase monopolar spindle 1; PD-1, programmed cell death receptor; CDK, cyclin-dependent kinase. Open table in a new tab i.v., intravenous; o.a., oral administration; mTOR, mammalian target of rapamycin; HDAC6, histone deacetylase 6; PD-L1, programmed cell death ligand 1; MPS1, serine/threonine kinase monopolar spindle 1; PD-1, programmed cell death receptor; CDK, cyclin-dependent kinase. PARP is a constitutively expressed nuclear enzyme that activates intracellular signaling pathways by transferring ADP-ribose from NAD+ to target proteins at the sites of DNA damage. Hence, PARP is involved in DNA repair, cellular proliferation, and oncogene regulation.44Audebert M. Salles B. Calsou P. Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining.J. Biol. Chem. 2004; 279: 55117-55126Abstract Full Text Full Text PDF PubMed Scopus (513) Google Scholar Various comprehensive reviews20Robson M. Im S.A. Senkus E. Xu B. Domchek S.M. Masuda N. Delaloge S. Li W. Tung N. Armstrong A. et al.Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.N. Engl. J. Med. 2017; 377: 523-533Crossref PubMed Scopus (1191) Google Scholar,36Farmer H. McCabe N. Lord C.J. Tutt A.N.J. Johnson D.A. Richardson T.B. Santarosa M. Dillon K.J. Hickson I. Knights C. et al.Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature. 2005; 434: 917-921Crossref PubMed Scopus (4153) Google Scholar,45Calabrese C.R. Almassy R. Barton S. Batey M.A. Calvert A.H. Canan-Koch S. Durkacz B.W. Hostomsky Z. Kumpf R.A. Kyle S. et al.Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361.J. Natl. Cancer Inst. 2004; 96: 56-67Crossref PubMed Google Scholar,46Turner N.C. Lord C.J. Iorns E. Brough R. Swift S. Elliott R. Rayter S. Tutt A.N. Ashworth A. A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor.EMBO J. 2008; 27: 1368-1377Crossref PubMed Scopus (260) Google Scholar have proposed" @default.
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• W3182636721 title "Circular RNA: A potential diagnostic, prognostic, and therapeutic biomarker for human triple-negative breast cancer" @default.
• W3182636721 cites W1045121760 @default.
• W3182636721 cites W1758946369 @default.
• W3182636721 cites W1963731933 @default.
• W3182636721 cites W1966173991 @default.
• W3182636721 cites W1966411071 @default.
• W3182636721 cites W1967791012 @default.
• W3182636721 cites W1969346276 @default.
• W3182636721 cites W1973268287 @default.
• W3182636721 cites W1981726010 @default.
• W3182636721 cites W1984119576 @default.
• W3182636721 cites W1985638918 @default.
• W3182636721 cites W1988163167 @default.
• W3182636721 cites W1989654872 @default.
• W3182636721 cites W1993529637 @default.
• W3182636721 cites W2012116166 @default.
• W3182636721 cites W2017919052 @default.
• W3182636721 cites W2019230794 @default.
• W3182636721 cites W2023297465 @default.
• W3182636721 cites W2026570544 @default.
• W3182636721 cites W2027379868 @default.
• W3182636721 cites W2031593782 @default.
• W3182636721 cites W2037691883 @default.
• W3182636721 cites W2054891772 @default.
• W3182636721 cites W2055493067 @default.
• W3182636721 cites W2055920203 @default.
• W3182636721 cites W2058615001 @default.
• W3182636721 cites W2058835062 @default.
• W3182636721 cites W2059191987 @default.
• W3182636721 cites W2063382533 @default.
• W3182636721 cites W2069282082 @default.
• W3182636721 cites W2082887122 @default.
• W3182636721 cites W2085898732 @default.
• W3182636721 cites W2094813328 @default.
• W3182636721 cites W2096027508 @default.
• W3182636721 cites W2096283457 @default.
• W3182636721 cites W2100155969 @default.
• W3182636721 cites W2100457669 @default.
• W3182636721 cites W2107931058 @default.
• W3182636721 cites W2110971908 @default.
• W3182636721 cites W2111495238 @default.
• W3182636721 cites W2116144791 @default.
• W3182636721 cites W2117964602 @default.
• W3182636721 cites W2132546029 @default.
• W3182636721 cites W2135800076 @default.
• W3182636721 cites W2135967835 @default.
• W3182636721 cites W2137315132 @default.
• W3182636721 cites W2137840425 @default.
• W3182636721 cites W2138929540 @default.
• W3182636721 cites W2142288805 @default.
• W3182636721 cites W2142577868 @default.
• W3182636721 cites W2147415463 @default.
• W3182636721 cites W2147806662 @default.
• W3182636721 cites W2149574104 @default.
• W3182636721 cites W2155464214 @default.
• W3182636721 cites W2157285286 @default.
• W3182636721 cites W2161382947 @default.
• W3182636721 cites W2170602872 @default.
• W3182636721 cites W2173858545 @default.
• W3182636721 cites W2194134194 @default.
• W3182636721 cites W2195191237 @default.
• W3182636721 cites W2261992653 @default.
• W3182636721 cites W2266356262 @default.
• W3182636721 cites W2285247593 @default.
• W3182636721 cites W2300229781 @default.
• W3182636721 cites W2302185643 @default.
• W3182636721 cites W2341291028 @default.
• W3182636721 cites W2345415641 @default.
• W3182636721 cites W2402636472 @default.
• W3182636721 cites W2430731787 @default.
• W3182636721 cites W2511152819 @default.
• W3182636721 cites W2531297636 @default.
• W3182636721 cites W2547310148 @default.
• W3182636721 cites W2566747056 @default.
• W3182636721 cites W2592259136 @default.
• W3182636721 cites W2592988313 @default.
• W3182636721 cites W2600581473 @default.
• W3182636721 cites W2606970705 @default.
• W3182636721 cites W2621271973 @default.
• W3182636721 cites W2622613223 @default.
• W3182636721 cites W2698251442 @default.
• W3182636721 cites W2735278122 @default.
• W3182636721 cites W2747105326 @default.
• W3182636721 cites W2752880228 @default.
• W3182636721 cites W2763042654 @default.
• W3182636721 cites W2765658585 @default.
• W3182636721 cites W2766581433 @default.
• W3182636721 cites W2766969050 @default.

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