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2000
Volume 20, Issue 5
  • ISSN: 1574-8928
  • E-ISSN: 2212-3970

Abstract

Background

Triple-negative breast cancer (TNBC) has a poor prognosis with current treatment options. Novel therapeutic strategies are urgently needed to enhance treatment outcomes for TNBC.

Objective

This study evaluated the efficacy of a three-agent regimen compared to existing treatment regimens in a TNBC mouse model, and elucidated its potential mechanisms of action.

Methods

TNBC xenograft tumor mouse model was established using a 4T1 cell line in female BALB/c mice. Mice were treated with the three-agent regimen and other comparative treatments. Tumor volume was monitored to assess the anti-tumor effects. Biochemical and pathological evaluations were conducted to examine the impact of the regimen on anti-tumor immunity, anti-tumor angiogenesis, and tumor cell apoptosis.

Results

The three-agent regimen consisting of SIN+BEV+PAB demonstrated significant anti-tumor efficacy compared to controls, PAB alone, SIN+PAB, and BEV+PAB groups from day 9 of drug administration. The superior anti-tumor effect of SIN+BEV+PAB was primarily attributed to enhanced anti-tumor immunity, evidenced by increased percentages of CD4+ and CD8+ T cells, elevated IFN-γ levels, and decreased percentages of Tregs, reduced levels of TGF-β, IL-6, and IL-10. Additionally, the regimen showed potent anti-angiogenic effects by reducing VEGF expression and micro vessel density (MVD). Furthermore, it promoted tumor cell apoptosis through upregulation of BAX and cleaved caspase3, while downregulating Bcl2.

Conclusion

These findings suggest that the novel three-agent combination of SIN+BEV+PAB may prove beneficial in improving treatment outcomes for patients with TNBC. The development of this regimen, which may be eligible for patent protection, could facilitate its introduction as a new therapeutic option for advanced TNBC in clinical practice.

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References

  1. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.2176336633525
     [Google Scholar]
  2. TorreL.A. SiegelR.L. WardE.M. JemalA. Global Cancer Incidence and Mortality Rates and Trends—An Update.Cancer Epidemiol. Biomarkers Prev.2016251162710.1158/1055‑9965.EPI‑15‑057826667886
     [Google Scholar]
  3. FoulkesW.D. SmithI.E. Reis-FilhoJ.S. Triple-negative breast cancer.N. Engl. J. Med.2010363201938194810.1056/NEJMra100138921067385
     [Google Scholar]
  4. BianchiniG. De AngelisC. LicataL. GianniL. Treatment landscape of triple-negative breast cancer — expanded options, evolving needs.Nat. Rev. Clin. Oncol.20221929111310.1038/s41571‑021‑00565‑234754128
     [Google Scholar]
  5. Leon-FerreR.A. GoetzM.P. Advances in systemic therapies for triple negative breast cancer.BMJ2023381e07167410.1136/bmj‑2022‑07167437253507
     [Google Scholar]
  6. YardleyD.A. ColemanR. ConteP. CortesJ. BrufskyA. ShtivelbandM. YoungR. BengalaC. AliH. EakelJ. SchneeweissA. de la Cruz-MerinoL. WilksS. O’ShaughnessyJ. GlückS. LiH. MillerJ. BartonD. HarbeckN. tnAcity investigators nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial.Ann. Oncol.20182981763177010.1093/annonc/mdy20129878040
     [Google Scholar]
  7. WangB. SunT. ZhaoY. WangS. ZhangJ. WangZ. TengY.E. CaiL. YanM. WangX. JiangZ. PanY. LuoJ. ShaoZ. WuJ. GuoX. HuX. A randomized phase 3 trial of Gemcitabine or Nab-paclitaxel combined with cisPlatin as first-line treatment in patients with metastatic triple-negative breast cancer.Nat. Commun.2022131402510.1038/s41467‑022‑31704‑735821019
     [Google Scholar]
  8. RobertN.J. DiérasV. GlaspyJ. BrufskyA.M. BondarenkoI. LipatovO.N. PerezE.A. YardleyD.A. ChanS.Y.T. ZhouX. PhanS.C. O’ShaughnessyJ. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer.J. Clin. Oncol.201129101252126010.1200/JCO.2010.28.098221383283
     [Google Scholar]
  9. BrufskyA.M. HurvitzS. PerezE. SwamyR. ValeroV. O’NeillV. RugoH.S. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.J. Clin. Oncol.201129324286429310.1200/JCO.2010.34.125521990397
     [Google Scholar]
  10. DelalogeS. PérolD. CourtinardC. BrainE. AsselainB. BachelotT. DebledM. DierasV. CamponeM. LevyC. JacotW. LorgisV. VeyretC. DalencF. FerreroJ.M. UwerL. KerbratP. GoncalvesA. Mouret-ReynierM.A. PetitT. JouannaudC. VanlemmensL. ChenucG. GuesmiaT. RobainM. CailliotC. Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study.Ann. Oncol.20162791725173210.1093/annonc/mdw26027436849
     [Google Scholar]
  11. CortesJ. CesconD.W. RugoH.S. NoweckiZ. ImS.A. YusofM.M. GallardoC. LipatovO. BarriosC.H. HolgadoE. IwataH. MasudaN. OteroM.T. GokmenE. LoiS. GuoZ. ZhaoJ. AktanG. KarantzaV. SchmidP. LuisF. GonzaloG.A. DiegoK. RubenK. MatiasM. MirtaV. SallyB-H. StephenB. PhilipC. ShereneL. DhanushaS. AndreaG. DonatienneT. CarlosB. LeandroB. FabianoC. RuffoF.J. RobertoH. Domicio CarvalhoL. Fernando Cezar ToniazziL. Roberto OdebrechtR. Antonio OrlandoS.N. FelipeS. DavidC. DanielleC. CristianoF. XinniS. JoanneY. AlejandroA. CarlosG. ClaudioS. CesarS. EduardoY. AlvaroG.D. JesusS. PetraH. ZdenekK. BohuslavM. KatarinaP. JanaP. VesnaG. ErikJ. JeanetteJ. SorenL. TamasL. HerveB. IsabelleD. AnthonyG. Anne-ClaireH-B. LuisT. Jens-UweB. PeterF. DirkF. NadiaH. JensH. AnnaK.F.S. ChristianK. SibylleL. DianaL. Tjoung-WonP-S. Raquel VonS. PaulineW. LouisC. AvaK. Kai Cheong RogerN. PeterA. TiborC. ZsuzsannaK. LaszloL. KarolyM. GaborR. JohnC. CatherineK. SeamusO.R. SaverioC. AntoniettaD.A. EnricoR. TomoyukiA. TakaakiF. KenichiI. TakashiI. YoshinoriI. TsutomuI. HirojiI. YoshimasaK. KojiM. YasuoM. HirofumiM. SeigoN. NaokiN. ShoichiroO. AkihikoO. YasuakiS. EijiS. MasatoT. YukoT. KenjiT. KoichiroT. JunichiroW. NaohitoY. YutakaY. TeruoY. AnitaB. MasturaM.Y. AngelG.V. AlejandroJ.R. JorgeM.R. FlaviaM-V. JessicaR.C. KarinB. VivianneT-H. DavidP. EwaC. EwaN-Z. ZbigniewN. BarbaraR. JoannaS. CezaryS. RafalT. BogdanZ. AlexanderA. NataliaF. OlegL. AndreyM. VladimirM. GuzelM. Jin HeeA. Seock-AhI. Keun SeokL. Kwong HwaP. Yeon HeeP. BegonaB.H. JavierC. JosefinaC.J. LuisC.M. JoseG.S. MariaG. EstherH. EstherZ.A. Chien-TingL. Mei-ChingL. Chiun-ShengH. Chao-JungT. Ling-MingT. CagatayA. GulB. IrfanC. ErhanG. SeydaG. NilM.M. MustafaO. OzgurO. SinanY. SteveC. JanineG. IainM.P. PeterS. NicholasT. MarkT. ChristopherT. DuncanW. HryhoriyA. OleksandrB. IgorB. OleksiiK. OlenaK. HannaK. AnnaK. IuriiL. AllaN. NatalyaO. OlgaP. AndriiR. SergiiS. YaroslavS. DmytroT. GrygoriiU. IhorV. SibelB. MadhuC. MichaelC. PatrickC. ScottC. JenniferD. KeerthiG. JeffreyH. KentH. WilliamI. RandaL. JaniceL. RaulM. SusanM. RitaN. IraO. CoralO. TimothyP. AmitP. BrianP. HopeR. IrinaR. MichaelS. RobertS. MichaelS. LauraS. BradleyS. MichaelaT. FrancesV-A. KEYNOTE-355 Investigators Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.Lancet2020396102651817182810.1016/S0140‑6736(20)32531‑933278935
     [Google Scholar]
  12. SchmidP. RugoH.S. AdamsS. SchneeweissA. BarriosC.H. IwataH. DiérasV. HenschelV. MolineroL. ChuiS.Y. MaiyaV. HusainA. WinerE.P. LoiS. EmensL.A. IMpassion130 Investigators Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol.2020211445910.1016/S1470‑2045(19)30689‑831786121
     [Google Scholar]
  13. MilesD. GligorovJ. AndréF. CameronD. SchneeweissA. BarriosC. XuB. WardleyA. KaenD. AndradeL. SemiglazovV. ReinischM. PatelS. PatreM. MoralesL. PatelS.L. KaulM. BarataT. O’ShaughnessyJ. ZhangQ. XuB. ShaoZ. WangX. GengC. YanX. TongZ. ShenK. YinY. SunT. YangJ. FengJ. YanM. WangY. LiuQ. ZhangS. De LaurentiisM. SantoroA. GuarneriV. ColleoniM. NatoliC. CortesiL. PlacidoS. GianniL. FerrauF. LiviL. ZambelliA. Del MastroL. ToniniG. MontemurroF. BianchiG. PedersiniR. PreteS. AllegriniG. NasoG. ViciP. LoiratD. MailliezA. PriouF. TredanO. DalencF. PerrinC. GligorovJ. Timar DavidM. DohollouN. TeixeiraL. BrocardF. ArnaudA. DelalogeS. SpanoJ-P. MansiL. AndradeL. DamianF. PedriniJ. AleixoS. HeggR. JuniorR. ReinischM. SchmidtM. WenzelC. GrischkeE-M. SchneeweissA. JustM. HarbeckN. SchumacherC. PetersU. FischerD. ForstbauerH. LierschR. WarnerE. BouganimN. DoyleC. Price HillerJ. VandenbergT. PavicM. RobinsonA. Roldan UrgoitiG. CalifarettiN. AlacaciogluA. GumusM. YalcinB. CicinI. KoseF. UygunK. KaplanM. CubukcuE. WardleyA. HarriesM. MilesD. DovalD. GuptaS. MohapatraP. ChatterjeeS. GhadyalpatilN. SinghalM. NagS. AgarwalA. WolfI. Gal YamE. YerushalmiR. PeretzT. FriedG. Ben BaruchN. KatzD. HamiltonE. KayaliF. BrufskyA. TelliM. WrightG. OyolaR. RakowskiT. GraffS. TjulandinS. SemiglazovV. AparicioA. Ruiz BorregoM. MerinoL. Guerra MartinezJ. LopezE. YamashitaT. OhtaniS. InoueK. ItoY. NiikuraN. NakayamaT. SagaraY. YanagitaY. KamadaY. KanekoK. KaenD. NervoA. EniuA. SchenkerM. PriesterP. MelicharB. ZimovjanovaM. SormovaP. SufliarskyJ. KakalejcikM. BelbarakaR. ErrihaniH. Le ThanD. PhamD. AravantinosG. PapadimitriouC. KoumakisG. PapandreouC. PodolskiP. TabaneK. IMpassion131 investigators Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer.Ann. Oncol.2021328994100410.1016/j.annonc.2021.05.80134219000
     [Google Scholar]
  14. JiangZ. OuyangQ. SunT. ZhangQ. TengY. CuiJ. WangH. YinY. WangX. ZhouX. WangY. SunG. WangJ. ZhangL. YangJ. QianJ. YanM. LiuX. YiT. ChengY. LiM. ZangA. WangS. WangC. WuX. ChengJ. LiH. LinY. GengC. GuK. XieC. XiongH. WuX. YangJ. LiQ. ChenY. LiF. ZhangA. ZhangY. WuY. NieJ. LiuQ. WangK. MoX. ChenL. PanY. FuP. ZhangH. PangD. ShengY. HanY. WangH. CangS. LuoX. YuW. DengR. YangC. KeeganP. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.Nat. Med.202430124925610.1038/s41591‑023‑02677‑x38191615
     [Google Scholar]
  15. DattaM. CoussensL.M. NishikawaH. HodiF.S. JainR.K. Reprogramming the tumor microenvironment to improve immunotherapy: emerging strategies and combination therapies.Am. Soc. Clin. Oncol. Educ. Book2019393916517410.1200/EDBK_23798731099649
     [Google Scholar]
  16. TsavarisN. KosmasC. VadiakaM. KanelopoulosP. BoulamatsisD. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes.Br. J. Cancer2002871212710.1038/sj.bjc.660034712085250
     [Google Scholar]
  17. WimmerK. SachetM. RamosC. FrantalS. BirnleitnerH. BrostjanC. ExnerR. FilipitsM. Bago-HorvathZ. RudasM. BartschR. GnantM. SingerC.F. BalicM. EgleD. OehlerR. FitzalF. Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients.J. Exp. Clin. Cancer Res.202342130010.1186/s13046‑023‑02876‑x37957750
     [Google Scholar]
  18. HeinhuisK.M. RosW. KokM. SteeghsN. BeijnenJ.H. SchellensJ.H.M. Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors.Ann. Oncol.201930221923510.1093/annonc/mdy55130608567
     [Google Scholar]
  19. RolandC.L. LynnK.D. ToombsJ.E. DineenS.P. UdugamasooriyaD.G. BrekkenR.A. Cytokine levels correlate with immune cell infiltration after anti-VEGF therapy in preclinical mouse models of breast cancer.PLoS One2009411e766910.1371/journal.pone.000766919888452
     [Google Scholar]
  20. WangQ. GaoJ. DiW. WuX. Anti-angiogenesis therapy overcomes the innate resistance to PD-1/PD-L1 blockade in VEGFA-overexpressed mouse tumor models.Cancer Immunol. Immunother.20206991781179910.1007/s00262‑020‑02576‑x32347357
     [Google Scholar]
  21. SocinskiM.A. NishioM. JotteR.M. CappuzzoF. OrlandiF. StroyakovskiyD. NogamiN. Rodríguez-AbreuD. Moro-SibilotD. ThomasC.A. BarlesiF. FinleyG. KongS. LeeA. ColemanS. ZouW. McClelandM. ShankarG. ReckM. IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC.J. Thorac. Oncol.202116111909192410.1016/j.jtho.2021.07.00934311108
     [Google Scholar]
  22. RiniB.I. PowlesT. AtkinsM.B. EscudierB. McDermottD.F. SuarezC. BracardaS. StadlerW.M. DonskovF. LeeJ.L. HawkinsR. RavaudA. AlekseevB. StaehlerM. UemuraM. De GiorgiU. MelladoB. PortaC. MelicharB. GurneyH. BedkeJ. ChoueiriT.K. ParnisF. KhaznadarT. ThobhaniA. LiS. Piault-LouisE. FrantzG. HuseniM. SchiffC. GreenM.C. MotzerR.J. IMmotion151 Study Group Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial.Lancet2019393101892404241510.1016/S0140‑6736(19)30723‑831079938
     [Google Scholar]
  23. GalleP.R. FinnR.S. QinS. IkedaM. ZhuA.X. KimT.Y. KudoM. BrederV. MerleP. KasebA. LiD. MullaS. VerretW. XuD.Z. HernandezS. DingB. LiuJ. HuangC. LimH.Y. ChengA.L. DucreuxM. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial.Lancet Oncol.2021227991100110.1016/S1470‑2045(21)00151‑034051880
     [Google Scholar]
  24. RedmondP.H. Method of treating triple negative breast cancer.United States Patent 10736902 2020
  25. QinY. DengJ. ZhangL. YuanJ. YangH. LiQ. Tumor microenvironment characterization in triple-negative breast cancer identifies prognostic gene signature.Aging (Albany NY)20211345485550510.18632/aging.20247833536349
     [Google Scholar]
  26. KashyapD. BalA. IrinikeS. KhareS. BhattacharyaS. DasA. SinghG. Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer.Appl. Immunohistochem. Mol. Morphol.202331853354310.1097/PAI.000000000000113937358863
     [Google Scholar]
  27. SzulcA. WoźniakM. Targeting pivotal hallmarks of cancer for enhanced therapeutic strategies in triple-negative breast cancer treatment in vitro, in vivo and clinical trials literature review.Cancers2024168148310.3390/cancers1608148338672570
     [Google Scholar]
  28. PietenpolJ.A. Markers of triple-negative breast cancer and uses thereof.United States Patent 11788147 2023
  29. Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins.United States Patent 11872205 2024
  30. BaillyC. ThuruX. QuesnelB. Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times.NAR Cancer202021zcaa00210.1093/narcan/zcaa00234316682
     [Google Scholar]
  31. SukumarJ. GastK. QuirogaD. LustbergM. WilliamsN. Triple-negative breast cancer: promising prognostic biomarkers currently in development.Expert Rev. Anticancer Ther.202121213514810.1080/14737140.2021.184098433198517
     [Google Scholar]
  32. ZhengX. FangZ. LiuX. DengS. ZhouP. WangX. ZhangC. YinR. HuH. ChenX. HanY. ZhaoY. LinS.H. QinS. WangX. KimB.Y.S. ZhouP. JiangW. WuQ. HuangY. Increased vessel perfusion predicts the efficacy of immune checkpoint blockade.J. Clin. Invest.201812852104211510.1172/JCI9658229664018
     [Google Scholar]
  33. MotzG.T. SantoroS.P. WangL.P. GarrabrantT. LastraR.R. HagemannI.S. LalP. FeldmanM.D. BenenciaF. CoukosG. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors.Nat. Med.201420660761510.1038/nm.354124793239
     [Google Scholar]
  34. HegdeP.S. WallinJ.J. MancaoC. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics.Semin. Cancer Biol.201852Pt 211712410.1016/j.semcancer.2017.12.00229229461
     [Google Scholar]
  35. ShrimaliR.K. YuZ. TheoretM.R. ChinnasamyD. RestifoN.P. RosenbergS.A. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer.Cancer Res.201070156171618010.1158/0008‑5472.CAN‑10‑015320631075
     [Google Scholar]
  36. GeorganakiM. van HoorenL. DimbergA. Vascular Targeting to Increase the Efficiency of Immune Checkpoint Blockade in Cancer.Front. Immunol.20189308110.3389/fimmu.2018.0308130627131
     [Google Scholar]
  37. ZhuP. HuC. HuiK. JiangX. The role and significance of VEGFR2+ regulatory T cells in tumor immunity.OncoTargets Ther.2017104315431910.2147/OTT.S14208528919780
     [Google Scholar]
  38. TianL. GoldsteinA. WangH. Ching LoH. Sun KimI. WelteT. ShengK. DobroleckiL.E. ZhangX. PutluriN. PhungT.L. ManiS.A. StossiF. SreekumarA. ManciniM.A. DeckerW.K. ZongC. LewisM.T. ZhangX.H.F. Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming.Nature2017544764925025410.1038/nature2172428371798
     [Google Scholar]
  39. SongY. FuY. XieQ. ZhuB. WangJ. ZhangB. Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.Front. Immunol.202011195610.3389/fimmu.2020.0195632983126
     [Google Scholar]
  40. TartourE. PereH. MaillereB. TermeM. MerillonN. TaiebJ. SandovalF. Quintin-ColonnaF. LacerdaK. KaradimouA. BadoualC. TedguiA. FridmanW.H. OudardS. Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy.Cancer Metastasis Rev.2011301839510.1007/s10555‑011‑9281‑421249423
     [Google Scholar]
  41. DingS. QiaoN. ZhuQ. TongY. WangS. ChenX. TianQ. XiaoY. ShenK. Single-cell atlas reveals a distinct immune profile fostered by T-cell B-cell crosstalk in triple negative breast cancer.Cancer Commun. (Lond.)202343666168410.1002/cac2.1242937158690
     [Google Scholar]
  42. BeckersR.K. SelingerC.I. VilainR. MadoreJ. WilmottJ.S. HarveyK. HollidayA. CooperC.L. RobbinsE. GillettD. KennedyC.W. GluchL. CarmaltH. MakC. WarrierS. GeeH.E. ChanC. McLeanA. WalkerE. McNeilC.M. BeithJ.M. SwarbrickA. ScolyerR.A. O’TooleS.A. Programmed death ligand 1 expression in triple negative breast cancer is associated with tumour infiltrating lymphocytes and improved outcome.Histopathology2016691253410.1111/his.1290426588661
     [Google Scholar]
  43. AgostinettoE. LosurdoA. Nader-MartaG. SantoroA. PunieK. BarrosoR. PopovicL. SolinasC. KokM. de AzambujaE. LambertiniM. Progress and pitfalls in the use of immunotherapy for patients with triple negative breast cancer.Expert Opin. Investig. Drugs202231656759110.1080/13543784.2022.204923235240902
     [Google Scholar]
  44. HuangP. ZhouX. ZhengM. YuY. JinG. ZhangS. Regulatory T cells are associated with the tumor immune microenvironment and immunotherapy response in triple-negative breast cancer.Front. Immunol.202314126353710.3389/fimmu.2023.126353737767092
     [Google Scholar]
  45. FattoriS. Le RoyA. HouacineJ. RobertL. AbesR. GorvelL. GranjeaudS. RouvièreM.S. Ben AmaraA. BoucheritN. TarpinC. PakradouniJ. Charafe-JauffretE. HouvenaeghelG. LambaudieE. BertucciF. RochigneuxP. GonçalvesA. FoussatA. ChrétienA.S. OliveD. CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer.Cancer Res.202383183026304410.1158/0008‑5472.CAN‑23‑061337379438
     [Google Scholar]
  46. El BairiK. HaynesH.R. BlackleyE. FinebergS. ShearJ. TurnerS. de FreitasJ.R. SurD. AmendolaL.C. GharibM. KallalaA. ArunI. Azmoudeh-ArdalanF. FujimotoL. SuaL.F. LiuS.W. LienH.C. KirtaniP. BalancinM. El AttarH. GuleriaP. YangW. ShashE. ChenI.C. BautistaV. Do Prado MouraJ.F. RapoportB.L. CastanedaC. SpenglerE. Acosta-HaabG. FrahmI. SanchezJ. CastilloM. BouchmaaN. Md ZinR.R. ShuiR. OnyumaT. YangW. HusainZ. Willard-GalloK. CoosemansA. PerezE.A. ProvenzanoE. EricssonP.G. RichardetE. MehrotraR. SaranconeS. EhingerA. RimmD.L. BartlettJ.M.S. VialeG. DenkertC. HidaA.I. SotiriouC. LoiblS. HewittS.M. BadveS. SymmansW.F. KimR.S. PruneriG. GoelS. FrancisP.A. InurrigarroG. YamaguchiR. Garcia-RivelloH. HorlingsH. AfqirS. SalgadoR. AdamsS. KokM. DieciM.V. MichielsS. DemariaS. LoiS. El BairiK. HaynesH.R. BlackleyE. FinebergS. ShearJ. TurnerS. de FreitasJ.R. SurD. AmendolaL.C. GharibM. KallalaA. ArunI. Azmoudeh-ArdalanF. FujimotoL. SuaL.F. LiuS-W. LienH-C. KirtaniP. BalancinM. El AttarH. GuleriaP. YangW. ShashE. ChenI-C. BautistaV. Do Prado MouraJ.F. RapoportB.L. CastanedaC. SpenglerE. Acosta-HaabG. FrahmI. SanchezJ. CastilloM. BouchmaaN. Md ZinR.R. ShuiR. OnyumaT. YangW. HusainZ. Willard-GalloK. CoosemansA. PerezE.A. ProvenzanoE. EricssonP.G. RichardetE. MehrotraR. SaranconeS. EhingerA. RimmD.L. BartlettJ.M.S. VialeG. DenkertC. HidaA.I. SotiriouC. LoiblS. HewittS.M. BadveS. SymmansW.F. KimR.S. PruneriG. GoelS. FrancisP.A. InurrigarroG. YamaguchiR. Garcia-RivelloH. HorlingsH. AfqirS. SalgadoR. AdamsS. KokM. DieciM.V. MichielsS. DemariaS. LoiS. SchelfhoutV. ArbzadehE. BondanarA. ReyesS.A.G. RuzJ.R. KangJ. XiangL. ZimovjanovaM. TogoresP. OzturkT. PatilA. CorpaM. WhitehouseA. TanB. de PaulaA. RossettiC. Lang-SchwarzC. MahonS. GiacomettiC. LinderholmB. DemanF. MontagnaG. GongG. PavcovichM. ChaerY. CabreroI.A. de BritoM.L. IlievaN. FulopA. SouzaM. BilanciaD. IdowuM. JohriR. SzporJ. BachaniL. SchmittF. GiannottiM. KurebayashiY. RamirezB.E.A. SalidoE. BortesiL. BonettoS. ElominaK. LopezP. SharmaV. EdirisingheA. MathurD. SahayA. MouloudM.A. GiangC.H. MukolweE. KirukaE. SambergN. AbeN. BrownM. MillarE. LiX. YuanZ. PasupathyA. MieleR. LuffR. e PorfirioM.M.A. AjembaO. SoniR. OrvietoE. DiMaioM. ThomasJ. MerardR. SubramaniamM.M. ApolinarioT. PredaO. PredaR. MakangaA. MaiorM.S. LiL. SaghatchianM. SaurineT. JanssenE. CochranJ. VladaN. CappellessoR. ElferK. HollickM. DesaiS. OnerG. SchreursA. LiuS. PereraR. MercurioP. GarciaF. HosnyK. MatsumotoH. van DeurzenC. BianchiniG. CobanI. JahangirA. RahmanA. StoverD. LuzP. MartelA. WaumansY. StenzingerA. CortesJ. DimitrovaP. NauwelaersI. VelascoM. FanF. AkturkG. FirerM. RoxanisI. SchneckM. WenH. CockenpotV. KonstantinovA. CalatravaA. VidyaM.N. ChoiH.J. JankP. ÇÏinenA.H. SabanathanD. FlorisG. HoeflmayerD. HamadaT. LaudusN. GrigoriadisA. PorcellatoI. AcsB. MigliettaF. ParrodiJ. ClunieD. CalhounB. LuF-I. LefevreA. TabbarahS. TranW. Garcia-murillasI. JelinicP. BoeckxC. SouzaS. CebolleroM.Ç. FelipE. RendonJ.L.S. El GabryE. SaltzJ. BriaE. GarufiG. HartmanJ. SebastianM. OlofssonH. KooremanL. CucheroussetJ. MathieuM-C. Ballesteros-MerinoC. SiziopikouP. FongJ. KleinM. QulisI.R.I. WesselingJ. BellolioE. ArayaJ.C. NaberS. CheangM. CastellanoI. AlesA. LaenkholmA-V. KulkaJ. QuinnC. SapinoA. AmendoeiraI. MarchioC. BraybrookeJ. Vincent-SalomonA. KorskiK. SofopoulosM. StovgaardE.I.S. BianchiS. Bago-HorvathZ. YuC. RegitnigP. HallS. KosZ. SantS. TilleJ-C. GallasB. BethmannD. SavasP. MendesL. SolerT. van SeijenM. GruossoT. QuintanaA. GiltnaneJ. Van den EyndenG. DuregonE. de CaboR. RecamoP.C. GabouryL. ZimmermanJ. PopC.S. WernickeA. WilliamsD. GillA. SolomonB. ThapaB. FarshidG. GilhamL. ChristieM. O’TooleS. HendryS. FoxS.B. LuenS.J. LakhaniS.R. FuchsT. JohnT. BrcicI. HainfellnerJ. SigurdL. PreusserM. PoortmansP. DecaluweA. CareyC. ColpaertC. LarsimontD. PeetersD. BroeckxG. van de VijverK. BuisseretL. DirixL. HertoghsM. PiccartM. IgnatiadisM. Van BockstalM. SirtaineN. VermeulenP. de WindR. DeclercqS. GevaertT. Haibe-KansB. NelsonB.H. WatsonP.H. LeungS. NielsenT. ShiL. BalslevE. ThagaardJ. AlmangushA. MakitieA. JoensuuH. LundinJ. DrubayD. RoblinE. AndreF. Penault-LlorcaF. LemonnierJ. AdamJ. Lacroix-TrikiM. TernesN. Radosevic-RobinN. KlaushenF. WeberK. HarbeckN. GluzO. WienertS. CserniG. VingianiA. CriscitielloC. SolinasC. CuriglianoG. KonishiE. SuzukiE. YoshikawaK. KawaguchiK. TakadaM. ToiM. IshidaM. ShibataN. SajiS. KogawaT. SakataniT. OkamotoT. MoriyaT. KataokaT. ShimoiT. SugieT. SugieT. MukoharaT. ShuY. KikawaY. KozukaY. SayedS. RahayuR. RamsaroopR. Senkus-KonefkaE. ChmielikE. CardosoF. RibeiroJ. ChanJ. DentR. MartinM. HagenC. GuerreroA. RojoF. ComermaL. NuciforoP. SerranoV.V. CámaeaV.P. SteenbruggenT. CiompiF. NederlofI. Jan Hudecek van der LaakJ. van den BergJ. VoorwerkL. van de VijverM. de MaakerM. LinnS. McKenzieH. SomaiahN. TuttA. SwantonC. HileyC. MooreD.A. HallJ.A. Le QuesneJ. JabbarK.A. al BakirM. HillsR. IrshadS. YuanY. LiZ. LiuM. KleinJ. FadareO. ThompsonA. LazarA.J. GownA. LoA. Garrido CastroA.C. MadabhushiA. MoreiraA. RichardsonA. BeckA.H. BellizziA.M. WolffA. HarbhajankaA. SharmaA. Cimino-MathewsA. SrinivasanA. SinghB. ChennubhotlaC.S. ChauhanC. DillonD.A. ZardavasD. JohnsonD.B. ThompsonA.E. BrogiE. ReisenbichlerE. HuangE. HirschF.R. McArthurH. ZiaiJ. BrockJ. KernerJ. ZhaJ. LennerzJ.K. CarterJ.M. Reis-FilhoJ. SparanoJ. BalkoJ.M. Pogue-GeileK. SteeleK.E. BlenmanK.R.M. AllisonK.H. PusztaiL. CooperL. EstradaV.M. FlowersM. RobsonM. RebelattoM.C. HannaM.G. GoetzM.P. KhojastehM. SandersM.E. ReganM.M. MisialekM. AmgadM. TungN. SinghR. HuangR. PierceR.H. Leon-FerreR. SwainS. ElyS. KimS-R. BedriS. PaikS. SchnittS. d’AlfonsT. KurkureU. BossuytV. TongW. WangY. Dos AnjosC.H. GaireF. Van DiestP.J. International Immuno-Oncology Biomarker Working Group The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.NPJ Breast Cancer20217115010.1038/s41523‑021‑00346‑134853355
     [Google Scholar]
  47. DengJ. LiuX. RongL. NiC. LiX. YangW. LuY. YanX. QinC. ZhangL. QinZ. IFNγ responsiveness of endothelial cells leads to efficient angiostasis in tumours involving down regulation of Dll4.J. Pathol.2014233217018210.1002/path.434024615277
     [Google Scholar]
  48. De PalmaM. BiziatoD. PetrovaT.V. Microenvironmental regulation of tumour angiogenesis.Nat. Rev. Cancer201717845747410.1038/nrc.2017.5128706266
     [Google Scholar]
  49. HuangY. YuanJ. RighiE. KamounW.S. AncukiewiczM. NezivarJ. SantosuossoM. MartinJ.D. MartinM.R. VianelloF. LeblancP. MunnL.L. HuangP. DudaD.G. FukumuraD. JainR.K. PoznanskyM.C. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy.Proc. Natl. Acad. Sci. USA201210943175611756610.1073/pnas.121539710923045683
     [Google Scholar]
  50. CarreteroR. SektiogluI.M. GarbiN. SalgadoO.C. BeckhoveP. HämmerlingG.J. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells.Nat. Immunol.201516660961710.1038/ni.315925915731
     [Google Scholar]
  51. FukumuraD. KloepperJ. AmoozgarZ. DudaD.G. JainR.K. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges.Nat. Rev. Clin. Oncol.201815532534010.1038/nrclinonc.2018.2929508855
     [Google Scholar]
  52. MelaiuO. VanniG. PortarenaI. PistoleseC.A. AnemonaL. PomellaS. BeiR. BuonomoO.C. RoselliM. MaurielloA. BarillariG. The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies.Int. J. Mol. Sci.2023244322610.3390/ijms2404322636834641
     [Google Scholar]
  53. KhanK.A. KerbelR.S. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa.Nat. Rev. Clin. Oncol.201815531032410.1038/nrclinonc.2018.929434333
     [Google Scholar]
  54. AshrafizadehM. MohammadinejadR. TavakolS. AhmadiZ. SahebkarA. New Insight into Triple-Negative Breast Cancer Therapy: The Potential Roles of Endoplasmic Reticulum Stress and Autophagy Mechanisms.Anticancer. Agents Med. Chem.202121667969110.2174/187152062066620061918071632560613
     [Google Scholar]
  55. AdinewG.M. MessehaS. TakaE. AhmedS.A. SolimanK.F.A. The Role of Apoptotic Genes and Protein-Protein Interactions in Triple-negative Breast Cancer.Cancer Genomics Proteomics202320324727210.21873/cgp.2037937093683
     [Google Scholar]
  56. LiuY. HongG. MaoL. SuZ. LiuT. LiuH. A Novel Paclitaxel Derivative for Triple-Negative Breast Cancer Chemotherapy.Molecules2023289366210.3390/molecules2809366237175072
     [Google Scholar]
  57. SorrentinoC. CiummoS.L. D’AntonioL. LanutiP. AbramsS.I. YinZ. LuL.F. Di CarloE. Hindering triple negative breast cancer progression by targeting endogenous interleukin 30 requires IFNγ signaling.Clin. Transl. Med.2021112e27810.1002/ctm2.27833635005
     [Google Scholar]
  58. KortylewskiM. YuH. Role of Stat3 in suppressing anti-tumor immunity.Curr. Opin. Immunol.200820222823310.1016/j.coi.2008.03.01018479894
     [Google Scholar]
  59. ParkS.K. ByunW.S. LeeS. HanY.T. JeongY.S. JangK. ChungS.J. LeeJ. SuhY.G. LeeS.K. A novel small molecule STAT3 inhibitor SLSI-1216 suppresses proliferation and tumor growth of triple-negative breast cancer cells through apoptotic induction.Biochem. Pharmacol.202017811405310.1016/j.bcp.2020.11405332450253
     [Google Scholar]
  60. LiJ. ZhangD. LiuZ. WangY. LiX. WangZ. LiangG. YuanX. LiY. KomorowskiA.L. RozenW.M. OrlandiA. TakabeK. FranceschiniG. JerusalemG. WangX. The combined effect and mechanism of antiangiogenic drugs and PD-L1 inhibitor on cell apoptosis in triple negative breast cancer.Ann. Transl. Med.20231128310.21037/atm‑22‑644636819490
     [Google Scholar]
  61. LiQ. WangY. JiaW. DengH. LiG. DengW. ChenJ. KimB.Y.S. JiangW. LiuQ. LiuJ. Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade.Clin. Cancer Res.20202671712172410.1158/1078‑0432.CCR‑19‑217931848190
     [Google Scholar]
  62. LiuJ. LiuQ. LiY. LiQ. SuF. YaoH. SuS. WangQ. JinL. WangY. LauW.Y. JiangZ. SongE. Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial.J. Immunother. Cancer202081e00069610.1136/jitc‑2020‑00069632448804
     [Google Scholar]
  63. LiuJ. LiY. LiQ. LiangD. WangQ. LiuQ. Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients.Breast Cancer Res. Treat.2021186368769710.1007/s10549‑021‑06128‑433634417
     [Google Scholar]
  64. ZhengH WuL ChenJ Neoadjuvant nivolumab plus bevacizumab therapy improves the prognosis of triple-negative breast cancer in humanized mouse models.Breast Cancer202431337138110.1007/s12282‑024‑01543‑z38289410
     [Google Scholar]
  65. ChenL. JiangY.Z. WuS.Y. WuJ. DiG.H. LiuG.Y. YuK.D. FanL. LiJ.J. HouY.F. HuZ. ChenC.M. HuangX.Y. CaoA.Y. HuX. ZhaoS. MaX.Y. XuY. SunX.J. ChaiW.J. GuoX. ChenX. XuY. ZhuX.Y. ZouJ.J. YangW.T. WangZ.H. ShaoZ.M. Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.Clin. Cancer Res.202228132807281710.1158/1078‑0432.CCR‑21‑431335247906
     [Google Scholar]
  66. WuS.Y. XuY. ChenL. FanL. MaX.Y. ZhaoS. SongX.Q. HuX. YangW.T. ChaiW.J. GuoX.M. ChenX.Z. XuY.H. ZhuX.Y. ZouJ.J. WangZ.H. JiangY.Z. ShaoZ.M. Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC: concept exploration and biomarker analysis in the FUTURE-C-Plus trial.Mol. Cancer20222118410.1186/s12943‑022‑01536‑635337339
     [Google Scholar]
  67. OzakiY. TsurutaniJ. MukoharaT. IwasaT. TakahashiM. TanabeY. KawabataH. MasudaN. FutamuraM. MinamiH. MatsumotoK. YoshimuraK. KitanoS. TakanoT. Safety and efficacy of nivolumab plus bevacizumab, paclitaxel for HER2-negative metastatic breast cancer: Primary results and biomarker data from a phase 2 trial (WJOG9917B).Eur. J. Cancer202217119320210.1016/j.ejca.2022.05.01435728379
     [Google Scholar]
  68. ZhangQ. ShaoB. TongZ. OuyangQ. WangY. XuG. LiS. LiH. A phase Ib study of camrelizumab in combination with apatinib and fuzuloparib in patients with recurrent or metastatic triple-negative breast cancer.BMC Med.202220132110.1186/s12916‑022‑02527‑636184642
     [Google Scholar]
  69. HanY. WangJ. SunT. OuyangQ. LiJ. YuanJ. XuB. Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer.Signal Transduct. Target. Ther.20238142910.1038/s41392‑023‑01672‑537973901
     [Google Scholar]
  70. PD-1/PD-L1 inhibitors for the treatment of cancer.United States Patent 10800846 2020
  71. Antibody molecules to PD-L1 and methods of treating cancer.United States Patent 10851165 2020
  72. Combination immunotherapy for treatment of triple-negative breast cancer.United States Patent 11564987 2023
  73. Multi-target drug candidates for the treatment of triple-negative breast cancer.United States Patent 11970464 2024
  74. Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer.United States Patent 10570202 2020
  75. KumariL. MishraL. PatelP. SharmaN. GuptaG.D. KurmiB.D. Emerging targeted therapeutic strategies for the treatment of triple-negative breast cancer.J. Drug Target.202331988990710.1080/1061186X.2023.224557937539789
     [Google Scholar]
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A Three-agent Regimen for Triple Negative Breast Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery 20, 776 (2025); https://doi.org/10.2174/0115748928350267250105153944
/content/journals/pra/10.2174/0115748928350267250105153944
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  • Article Type:     Research Article
Keyword(s): angiogenesis inhibitors; antineoplastic agents; immunotherapy; Triple negative breast neoplasms; tumor microenvironment; xenograft model antitumor assays

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