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2000
Volume 32, Issue 36
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Hormone signaling plays a significant role in cancerogenesis. This review presents a comprehensive analysis of FDA-approved drugs, as well as recent clinical trials of drugs acting on hormone signaling pathways. It discusses traditional methods of hormonal cancer therapy and identifies new mechanisms in cancer hormonal signaling. The review has made use of the databases Clinicaltrials.gov and PubMed to find new trends in the development of anti-cancer drugs and related hormonal-dependent mechanisms of breast cancer.

Methods

A search of the Drugs@FDA database was conducted to identify pharmaceutical agents approved by the FDA for the treatment of hormone-dependent breast tumors. The clinical trials for these drugs were obtained from ClinicalTrials.gov. The search was expanded from 2018 to early 2024. The keywords used in the search for information were breast cancer, hormonal signaling pathways, luminal types of breast cancer, and hormone-dependent breast cancer. The drug targets, pharmacological information, and clinical data were obtained from the PubMed database.

Results

An analysis of the ClinicalTrials.gov database revealed that the pharmacokinetic direction has significant potential for the discovery of new drugs. The metabolites of SERMs metabolites and their combination have the potential to enhance the efficiency of prodrug. Small molecules can penetrate through the blood-brain-barrier, making them a promising avenue for treating brain metastasis. New SERDs, such as ZB716, exhibit superior oral bioavailability compared to fulvestrant, which is solely administered injection. The investigation of the signaling hormonal pathways of BC allows for the enhancement of personalised anti-cancer therapy and the overcoming of resistance. Consequently, the specific mechanism of action of ARV-471 (the PROTAC group) enhances sensitivity to drug-resistant targets and affects non-enzymatic functions. Furthermore, PROTACs exhibit markedly enhanced target selectivity in comparison to traditional inhibitors. The combination of endocrine therapy for breast cancer with compounds that target mTOR, PI3K, CDK4/6, and other pathways holds considerable promise. The combination of letrozole with everolimus demonstrated the most promising outcome, with a median progression-free survival period of 22 months, a significant improvement over the 9-month median progression-free survival observed in monotherapy with letrozole.

Conclusion

It is evident that traditional endocrine treatments play a pivotal role in the management of HR+ BC. However, the emergence of resistance necessitates the development of novel therapeutic strategies. These strategies should be based on pharmacokinetics, further investigation of the molecular signaling pathways of BC, such as new SERMs, SERDs, PROTACs, as well as new drug groups, like SERCAs, CERANs, SHERPAs. Combination therapy represents the most promising avenue for BC treatment. While PROTAC combination with new monotherapeutic agents for BC treatment has yet to be investigated, we believe that such combinations have the potential to make the treatment more selective, effective, and personalised in the future.

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References

  1. BrayF. LaversanneM. SungH. FerlayJ. SiegelR.L. SoerjomataramI. JemalA. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202474322926310.3322/caac.2183438572751
     [Google Scholar]
  2. DaiD. WuH. ZhuangH. ChenR. LongC. ChenB. Genetic and clinical landscape of ER + /PR- breast cancer in China.BMC Cancer2023231118910.1186/s12885‑023‑11643‑238049758
     [Google Scholar]
  3. HowladerN. AltekruseS.F. LiC.I. ChenV.W. ClarkeC.A. RiesL.A.G. CroninK.A. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status.J. Natl. Cancer Inst.20141065dju05510.1093/jnci/dju05524777111
     [Google Scholar]
  4. BeatsonG.T. On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases.Trans. Med. Chir. Soc. Edinb.18961515317929584099
     [Google Scholar]
  5. Hormone therapy for cancer.Available from: https://about-cancer.cancerresearchuk.org/about-cancer/treatment/hormone-therapy/for-cancer
  6. KerdivelG. FlouriotG. PakdelF. Modulation of estrogen receptor alpha activity and expression during breast cancer progression.Vitam. Horm.20139313516010.1016/B978‑0‑12‑416673‑8.00004‑623810005
     [Google Scholar]
  7. ClusanL. FerrièreF. FlouriotG. PakdelF. A basic review on estrogen receptor signaling pathways in breast cancer.Int. J. Mol. Sci.2023247683410.3390/ijms2407683437047814
     [Google Scholar]
  8. LauK.H. TanA.M. ShiY. New and emerging targeted therapies for advanced breast cancer.Int. J. Mol. Sci.2022234228810.3390/ijms2304228835216405
     [Google Scholar]
  9. ŁukasiewiczS. Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—An updated review.Cancers20211317428710.3390/cancers13174287
     [Google Scholar]
  10. HaqueR. AhmedS.A. InzhakovaG. ShiJ. AvilaC. PolikoffJ. BernsteinL. EngerS.M. PressM.F. Impact of breast cancer subtypes and treatment on survival: An analysis spanning two decades.Cancer Epidemiol. Biomarkers Prev.201221101848185510.1158/1055‑9965.EPI‑12‑047422989461
     [Google Scholar]
  11. JohnsonK.S. ConantE.F. SooM.S. Molecular subtypes of breast cancer: A review for breast radiologists.J. Breast Imaging202131122410.1093/jbi/wbaa11038424845
     [Google Scholar]
  12. IacopettaD. CeramellaJ. BaldinoN. SinicropiM. CatalanoA. Targeting breast cancer: An overlook on current strategies.Int. J. Mol. Sci.2023244364310.3390/ijms2404364336835056
     [Google Scholar]
  13. MoisandA. MadéryM. BoyerT. DomblidesC. BlayeC. LarmonierN. Hormone receptor signaling and breast cancer resistance to anti-tumor immunity.Int. J. Mol. Sci.202324201504810.3390/ijms24201504837894728
     [Google Scholar]
  14. MendozaS.M. MontorM.J. Immune tumor microenvironment in breast cancer and the participation of estrogen and its receptors in cancer physiopathology.Front. Immunol.20191034810.3389/fimmu.2019.0034830881360
     [Google Scholar]
  15. LuoJ. LiuD. Does GPER really function as a G protein-coupled estrogen receptor in vivo?Front. Endocrinol.20201114810.3389/fendo.2020.0014832296387
     [Google Scholar]
  16. ChengM. MichalskiS. KommaganiR. Role for growth regulation by estrogen in breast cancer 1 (GREB1) in hormone-dependent cancers.Int. J. Mol. Sci.2018199254310.3390/ijms1909254330154312
     [Google Scholar]
  17. RaeJ.M. JohnsonM.D. ScheysJ.O. CorderoK.E. LariosJ.M. LippmanM.E. GREB1 is a critical regulator of hormone dependent breast cancer growth.Breast Cancer Res. Treat.200592214114910.1007/s10549‑005‑1483‑415986123
     [Google Scholar]
  18. ChanY.T. LaiA.C.Y. LinR.J. WangY.H. WangY.T. ChangW.W. WuH.Y. LinY.J. ChangW.Y. WuJ.C. YuJ.C. ChenY.J. YuA.L. GPER-induced signaling is essential for the survival of breast cancer stem cells.Int. J. Cancer202014661674168510.1002/ijc.3258831340060
     [Google Scholar]
  19. KampaM. LappanoR. GrandeF. RizzutiB. MaggioliniM. CastanasE. JacquotY. Promising perspectives of the antiproliferative GPER inverse agonist ERα17p in breast cancer.Cells202312465310.3390/cells1204065336831322
     [Google Scholar]
  20. CatalanoS. GiordanoC. PanzaS. ChemiF. BonofiglioD. LanzinoM. RizzaP. RomeoF. FuquaS.A.W. MaggioliniM. AndòS. BaroneI. Tamoxifen through GPER upregulates aromatase expression: A novel mechanism sustaining tamoxifen-resistant breast cancer cell growth.Breast Cancer Res. Treat.2014146227328510.1007/s10549‑014‑3017‑424928526
     [Google Scholar]
  21. RomancerL.M. PoulardC. CohenP. SentisS. RenoirJ.M. CorboL. Cracking the estrogen receptor’s posttranslational code in breast tumors.Endocr. Rev.201132559762210.1210/er.2010‑001621680538
     [Google Scholar]
  22. AmicisD.F. ChimentoA. MontaltoF.I. CasaburiI. SirianniR. PezziV. Steroid receptor signallings as targets for resveratrol actions in breast and prostate cancer.Int. J. Mol. Sci.2019205108710.3390/ijms2005108730832393
     [Google Scholar]
  23. EeckhouteJ. CarrollJ.S. GeistlingerT.R. ArzayusT.M.I. BrownM. A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer.Genes Dev.200620182513252610.1101/gad.144600616980581
     [Google Scholar]
  24. ZhouF.H. DowntonT. FreelanderA. HurwitzJ. CaldonC.E. LimE. CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective.Front. Cell Dev. Biol.202311114879210.3389/fcell.2023.114879237035239
     [Google Scholar]
  25. PaternotS. BockstaeleL. BisteauX. KookenH. CoulonvalK. RogerP. Rb inactivation in cell cycle and cancer: The puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase.Cell Cycle20109468969910.4161/cc.9.4.1061120107323
     [Google Scholar]
  26. PurohitL. JonesC. GonzalezT. CastrellonA. HusseinA. The role of CD4/6 inhibitors in breast cancer treatment.Int. J. Mol. Sci.2024252124210.3390/ijms2502124238279242
     [Google Scholar]
  27. ThiebautC. KonanH.P. GuerquinM.J. ChesnelA. LiveraG. RomancerL.M. DumondH. The role of ERα36 in development and tumor malignancy.Int. J. Mol. Sci.20202111411610.3390/ijms2111411632526980
     [Google Scholar]
  28. MannaP.R. StetsonC.L. SlominskiA.T. PruittK. Role of the steroidogenic acute regulatory protein in health and disease.Endocrine201651172110.1007/s12020‑015‑0715‑626271515
     [Google Scholar]
  29. MannaP.R. AhmedA.U. VartakD. MolehinD. PruittK. Overexpression of the steroidogenic acute regulatory protein in breast cancer: Regulation by histone deacetylase inhibition.Biochem. Biophys. Res. Commun.2019509247648210.1016/j.bbrc.2018.12.14530595381
     [Google Scholar]
  30. MannaP.R. RamachandranS. PradeepkiranJ.A. MolehinD. PiedrasC.I. PruittK. GanapathyV. ReddyP.H. Expression and function of StAR in cancerous and non-cancerous human and mouse breast tissues: New insights into diagnosis and treatment of hormone-sensitive breast cancer.Int. J. Mol. Sci.202324175810.3390/ijms2401075836614200
     [Google Scholar]
  31. WeissA. KingT.A. What is the role of neoadjuvant endocrine therapy for breast cancer?Adv. Surg.202256127528610.1016/j.yasu.2022.02.00836096572
     [Google Scholar]
  32. CuccinielloL. GerratanaL. MastroD.L. PuglisiF. Tailoring adjuvant endocrine therapy in early breast cancer: When, how, and how long?Cancer Treat. Rev.202211010244510.1016/j.ctrv.2022.10244535944419
     [Google Scholar]
  33. DustinD. GuG. FuquaS.A.W. ESR1 mutations in breast cancer.Cancer2019125213714372810.1002/cncr.3234531318440
     [Google Scholar]
  34. DasS. KulkarniS. SinghY. KumarP. TharejaS. Selective estrogen receptor modulators (SERMs) for the treatment of ER+ breast cancer: An overview.J. Mol. Struct.2022127013385310.1016/j.molstruc.2022.133853
     [Google Scholar]
  35. LippmanS.M. BrownP.H. Tamoxifen prevention of breast cancer: An instance of the fingerpost.J. Natl. Cancer Inst.199991211809181910.1093/jnci/91.21.180910547388
     [Google Scholar]
  36. FairchildA. TirumaniS.H. RosenthalM.H. HowardS.A. KrajewskiK.M. NishinoM. ShinagareA.B. JagannathanJ.P. RamaiyaN.H. Hormonal therapy in oncology: A primer for the radiologist.AJR Am. J. Roentgenol.20152046W620W63010.2214/AJR.14.1360426001251
     [Google Scholar]
  37. HongJ. HuangJ. ShenL. ZhuS. GaoW. WuJ. HuangO. HeJ. ZhuL. ChenW. LiY. ChenX. ShenK. A prospective, randomized study of Toremifene vs. tamoxifen for the treatment of premenopausal breast cancer: Safety and genital symptom analysis.BMC Cancer202020166310.1186/s12885‑020‑07156‑x32677982
     [Google Scholar]
  38. SteifensandF. GallwasJ. BauerschmitzG. GründkerC. Inhibition of metabolism as a therapeutic option for tamoxifen-resistant breast cancer cells.Cells2021109239810.3390/cells1009239834572047
     [Google Scholar]
  39. JeffreysS.A. PowterB. BalakrishnarB. MokK. SoonP. FrankenA. NeubauerH. Souzad.P. BeckerT.M. Endocrine resistance in breast cancer: The role of estrogen receptor stability.Cells202099207710.3390/cells909207732932819
     [Google Scholar]
  40. TeftW.A. MansellS.E. KimR.B. Endoxifen, the active metabolite of tamoxifen, is a substrate of the efflux transporter P-glycoprotein (multidrug resistance 1).Drug Metab. Dispos.201139355856210.1124/dmd.110.03616021148080
     [Google Scholar]
  41. ShanL. Molecular imaging and contrast agent database (MICAD).Available from: http://www.ncbi.nlm.nih.gov/books/NBK23503/ 2004
  42. LiL. ChangB. JiangX. FanX. LiY. LiT. WuS. ZhangJ. KariminiaS. LiQ. Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.BMC Cancer201818197710.1186/s12885‑018‑4878‑430314452
     [Google Scholar]
  43. DaviesC. PanH. GodwinJ. GrayR. ArriagadaR. RainaV. AbrahamM. AlencarV.H.M. BadranA. BonfillX. BradburyJ. ClarkeM. CollinsR. DavisS.R. DelmestriA. ForbesJ.F. HaddadP. HouM.F. InbarM. KhaledH. KielanowskaJ. KwanW.H. MathewB.S. MittraI. MüllerB. NicolucciA. PeraltaO. PernasF. PetruzelkaL. PienkowskiT. RadhikaR. RajanB. RubachM.T. TortS. UrrútiaG. ValentiniM. WangY. PetoR. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.Lancet2013381986980581610.1016/S0140‑6736(12)61963‑123219286
     [Google Scholar]
  44. BernsteinL. DeapenD. CerhanJ.R. SchwartzS.M. LiffJ. MaloneyM.E. PerlmanJ.A. FordL. Tamoxifen therapy for breast cancer and endometrial cancer risk.J. Natl. Cancer Inst.199991191654166210.1093/jnci/91.19.165410511593
     [Google Scholar]
  45. MustonenM.V.J. PyrhönenS. LehtinenK.P-L. Toremifene in the treatment of breast cancer.World J. Clin. Oncol.20145339340510.5306/wjco.v5.i3.39325114854
     [Google Scholar]
  46. LiX. LiZ. LiL. LiuT. QianC. RenY. LiZ. ChenK. JiD. ZhangM. WangJ. Toremifene, an alternative adjuvant endocrine therapy, is better than tamoxifen in breast cancer patients with CYP2D6*10 mutant genotypes.Cancer Res. Treat.202456113414210.4143/crt.2023.65237591782
     [Google Scholar]
  47. LuY. LiuW. Selective estrogen receptor degraders (SERDs): A promising strategy for estrogen receptor positive endocrine-resistant breast cancer.J. Med. Chem.20206324150941511410.1021/acs.jmedchem.0c0091333138369
     [Google Scholar]
  48. BoérK. Fulvestrant in advanced breast cancer: Evidence to date and place in therapy.Ther. Adv. Med. Oncol.20179746547910.1177/175883401771109728717399
     [Google Scholar]
  49. HernandoC. MorilloO.B. TapiaM. MoragónS. MartínezM.T. ErolesP. CanoG.I. ArtiguesA.A. LluchA. BermejoB. CejalvoJ.M. Oral selective estrogen receptor degraders (SERDs) as a novel breast cancer therapy: Present and future from a clinical perspective.Int. J. Mol. Sci.20212215781210.3390/ijms2215781234360578
     [Google Scholar]
  50. KaminskaK. AkrapN. StaafJ. AlvesC.L. EhingerA. EbbessonA. HedenfalkI. BeumersL. VeerlaS. HarbstK. EhmsenS. BorgquistS. BorgÅ. FidalgoP.A. DitzelH.J. BoschA. HonethG. Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer.Breast Cancer Res.20212312610.1186/s13058‑021‑01402‑133602273
     [Google Scholar]
  51. McDonnellD.P. WardellS.E. ChangC.Y. NorrisJ.D. Next-generation endocrine therapies for breast cancer.J. Clin. Oncol.202139121383138810.1200/JCO.20.0356533705209
     [Google Scholar]
  52. IorfidaM. MazzaM. MunzoneE. Fulvestrant in combination with CDK4/6 inhibitors for HER2- metastatic breast cancers: Current perspectives.Breast Cancer202012455610.2147/BCTT.S19624032256106
     [Google Scholar]
  53. ChangD.Y. MaW.L. LuY.S. Role of alpelisib in the treatment of PIK3CA-mutated breast cancer: Patient selection and clinical perspectives.Ther. Clin. Risk Manag.20211719320710.2147/TCRM.S25166833707948
     [Google Scholar]
  54. RatreP. MishraK. DubeyA. VyasA. JainA. TharejaS. Aromatase inhibitors for the treatment of breast cancer: A journey from the scratch.Anticancer. Agents Med. Chem.202020171994200410.2174/187152062066620062720410532593281
     [Google Scholar]
  55. ChumsriS. HowesT. BaoT. SabnisG. BrodieA. Aromatase, aromatase inhibitors, and breast cancer.J. Steroid Biochem. Mol. Biol.20111251-2132210.1016/j.jsbmb.2011.02.00121335088
     [Google Scholar]
  56. ChumsriS. Clinical utilities of aromatase inhibitors in breast cancer.Int. J. Womens Health2015749349910.2147/IJWH.S6990726005359
     [Google Scholar]
  57. BrodieA. NjarV. MacedoL.F. VasaitisT.S. SabnisG. The coffey lecture: Steroidogenic enzyme inhibitors and hormone dependent cancer.Urol. Oncol.2009271536310.1016/j.urolonc.2008.07.03619111799
     [Google Scholar]
  58. TentiS. CorrealeP. CheleschiS. FioravantiA. PirtoliL. Aromatase inhibitors—induced musculoskeletal disorders: Current knowledge on clinical and molecular aspects.Int. J. Mol. Sci.20202116562510.3390/ijms2116562532781535
     [Google Scholar]
  59. BhatnagarA.S. The discovery and mechanism of action of letrozole.Breast Cancer Res. Treat.2007105S171710.1007/s10549‑007‑9696‑317912633
     [Google Scholar]
  60. AlemrayatB. ElrayessM.A. AlanyR.G. ElhissiA. YounesH.M. Preparation and optimization of monodisperse polymeric microparticles using modified vibrating orifice aerosol generator for controlled delivery of letrozole in breast cancer therapy.Drug Dev. Ind. Pharm.201844121953196510.1080/03639045.2018.150329830035646
     [Google Scholar]
  61. AzandaryaniA.H. KashanianS. ShahlaeiM. DerakhshandehK. MotieiM. MoradiS. A comprehensive physicochemical, in vitro and molecular characterization of letrozole incorporated chitosan-lipid nanocomplex.Pharm. Res.20193646210.1007/s11095‑019‑2597‑430850895
     [Google Scholar]
  62. YassemiA. KashanianS. ZhalehH. Folic acid receptor-targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through induction of caspase-3 dependent-apoptosis for breast cancer treatment.Pharm. Dev. Technol.202025439740710.1080/10837450.2019.170373931893979
     [Google Scholar]
  63. KhanM.T. UddinZ. JavedM.A. ShahN. BashirH. ShaikhA.J. RajokaM.S.R. AmirzadaM.I. AsadM.H.H.B. PEGylated protamine letrozole nanoparticles: A promising strategy to combat human breast cancer via MCF-7 cell lines.BioMed Res. Int.20222022443851810.1155/2022/4438518
     [Google Scholar]
  64. SanfordM. PloskerG.L. Anastrozole.Drugs20086891319134010.2165/00003495‑200868090‑0000718547136
     [Google Scholar]
  65. BaoT. The clinical pharmacology of anastrozole.European Oncol. Haematol.20117210610810.17925/EOH.2011.07.02.106
     [Google Scholar]
  66. BaumM. BudzarA.U. CuzickJ. ForbesJ. HoughtonJ.H. KlijnJ.G.M. SahmoudT. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomised trial.Lancet200235993242131213910.1016/S0140‑6736(02)09088‑812090977
     [Google Scholar]
  67. UntchM. JackischC. Exemestane in early breast cancer: A review.Ther. Clin. Risk Manag.2008461295130410.2147/TCRM.S400719337436
     [Google Scholar]
  68. GhalyH.S.A. VaraminiP. New drug delivery strategies targeting the GnRH receptor in breast and other cancers.Endocr. Relat. Cancer20212811R251R26910.1530/ERC‑20‑044234236041
     [Google Scholar]
  69. RobertsonJ.F.R. BlameyR.W. The use of gonadotrophin-releasing hormone (GnRH) agonists in early and advanced breast cancer in pre- and perimenopausal women.Eur. J. Cancer200339786186910.1016/S0959‑8049(02)00810‑912706354
     [Google Scholar]
  70. ReyesH.M. NúñezM.G. SolisP.M.A. MuñozL.E. GuillénN. MarinO.J.C. RojasA.A. Treatment of breast cancer with gonadotropin-releasing hormone analogs.Front. Oncol.2019994310.3389/fonc.2019.0094331632902
     [Google Scholar]
  71. GuptaA. BandaruS. ManthriS. Goserelin ovarian ablation failure in premenopausal women with breast cancer.Cureus20211311e1960810.7759/cureus.1960834956746
     [Google Scholar]
  72. PerryC.M. BrogdenR.N. Goserelin.Drugs199651231934610.2165/00003495‑199651020‑000098808170
     [Google Scholar]
  73. FerraroE. WalshE.M. TaoJ.J. ChandarlapatyS. JhaveriK. Accelerating drug development in breast cancer: New frontiers for ER inhibition.Cancer Treat. Rev.202210910243210.1016/j.ctrv.2022.10243235839531
     [Google Scholar]
  74. ZafarE. MaqboolM.F. IqbalA. MaryamA. ShakirH.A. IrfanM. KhanM. LiY. MaT. A comprehensive review on anticancer mechanism of bazedoxifene.Biotechnol. Appl. Biochem.202269276778210.1002/bab.215033759222
     [Google Scholar]
  75. TsujiJ. LiT. GrinshpunA. CoorensT. RussoD. AndersonL. ReesR. NardoneA. PattersonC. LennonN.J. CibulskisC. LeshchinerI. TayobN. TolaneyS.M. TungN. McDonnellD.P. KropI.E. WinerE.P. StewartC. GetzG. JeselsohnR. Clinical efficacy and whole-exome sequencing of liquid biopsies in a phase IB/II study of bazedoxifene and palbociclib in advanced hormone receptor–positive breast cancer.Clin. Canc. Res.202228235066507810.1158/1078‑0432.CCR‑22‑2305
     [Google Scholar]
  76. JayaramanS. ReidJ.M. HawseJ.R. GoetzM.P. Endoxifen, an estrogen receptor targeted therapy: From bench to bedside.Endocrinology202116212bqab19110.1210/endocr/bqab19134480554
     [Google Scholar]
  77. DowntonT. ZhouF. SegaraD. JeselsohnR. LimE. Oral selective estrogen receptor degraders (SERDs) in breast cancer: Advances, challenges, and current status.Drug Des. Devel. Ther.2022162933294810.2147/DDDT.S38092536081610
     [Google Scholar]
  78. FructuosoG.I. BravoG.R. SchettiniF. Integrating new oral selective oestrogen receptor degraders in the breast cancer treatment.Curr. Opin. Oncol.202234663564210.1097/CCO.000000000000089236000362
     [Google Scholar]
  79. LloydM.R. WanderS.A. HamiltonE. RazaviP. BardiaA. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: Current and emerging role.Ther. Adv. Med. Oncol.2022141758835922111369410.1177/1758835922111369435923930
     [Google Scholar]
  80. FerroA. GeneraliD. CaffoO. CaldaraA. LisiD.D. DipasqualeM. LorenziM. MonteverdiS. FedeleP. CiribilliY. Oral selective estrogen receptor degraders (SERDs): The new emperors in breast cancer clinical practice?Semin. Oncol.2023503-59010110.1053/j.seminoncol.2023.08.00237673696
     [Google Scholar]
  81. BardiaA. EMERALD: Phase III trial of elacestrant (RAD1901) vs. endocrine therapy for previously treated ER+ advanced breast cancer.Future Oncol.2019152832093218
     [Google Scholar]
  82. LiangJ. ZbiegJ.R. BlakeR.A. ChangJ.H. DalyS. DiPasqualeA.G. FriedmanL.S. GelzleichterT. GillM. GiltnaneJ.M. GoodacreS. GuanJ. HartmanS.J. IngallaE.R. KategayaL. KieferJ.R. KleinheinzT. LabadieS.S. LaiT. LiJ. LiaoJ. LiuZ. ModyV. McLeanN. MetcalfeC. NanniniM.A. OehJ. O’RourkeM.G. OrtwineD.F. RanY. RayN.C. RousselF. SambroneA. SampathD. SchuttL.K. VinogradovaM. WaiJ. WangT. WertzI.E. WhiteJ.R. YeapS.K. YoungA. ZhangB. ZhengX. ZhouW. ZhongY. WangX. GDC-9545 (Giredestrant): A potent and orally bioavailable selective estrogen receptor antagonist and degrader with an exceptional preclinical profile for ER+ breast cancer.J. Med. Chem.20216416118411185610.1021/acs.jmedchem.1c0084734251202
     [Google Scholar]
  83. GantiA. YuS. SharpnackD. IngallaE. BruynD.T. Physiologically-based pharmacokinetic/pharmacodynamic modeling to predict tumor growth inhibition and the efficacious dose of selective estrogen receptor degraders in humans.Biopharm. Drug Dispos.202344430131410.1002/bdd.235837102506
     [Google Scholar]
  84. JimenezM.M. LimE. GregorC.M.M. BardiaA. WuJ. ZhangQ. NoweckiZ. CruzF. SafinR. KimS-B. SchemC. MonteroA. KhanS. BandyopadhyayR. ShivhareM. PatreM. MartinalboJ. RoncoroniL. MorenoP.P.D. SohnJ. 211MO Giredestrant (GDC-9545) vs. physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study.Ann. Oncol.202233S633S63410.1016/j.annonc.2022.07.250
     [Google Scholar]
  85. BardiaA. Abstract OT2-11-09: Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs. physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC).Canc. Res.202282S4OT211
     [Google Scholar]
  86. HurvitzS.A. QuirogaV. ParkY.H. BardiaA. ValverdeL.V. SteinseiferJ. FernandoT.M. SperaG. XueC. FaschingP.A. Abstract PD13-06: Neoadjuvant giredestrant (GDC-9545) + palbociclib versus anastrozole + palbociclib in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer: Primary analysis of the randomized, open-label, phase II coopERA breast cancer study.Cancer Res.202282PD13PD0610.1158/1538‑7445.SABCS21‑ES1‑3
     [Google Scholar]
  87. BardiaA. FernandoT.M. FaschingP.A. GarciaQ.V. ParkY.H. GiltnaneJ.M. XueC. ValverdeL.V. SzaboS.J. MorenoP.P.D. MooreH.M. HurvitzS.A. 144P Neoadjuvant giredestrant (GDC-9545) + palbociclib (P) vs. anastrozole (A) + P in postmenopausal women with oestrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Biomarker subgroup analysis of the randomised, phase II coopERA BC study.Ann. Oncol.202233S605S60610.1016/j.annonc.2022.07.179
     [Google Scholar]
  88. NeilanT.G. Abstract P5-18-07: Heart rate changes, cardiac safety, and exercise tolerance from a phase Ia/b study of giredestrant (GDC-9545)±palbociclib in patients with estrogen receptor-positive, HER2-negative locally advanced/metastatic breast cancer.Canc. Res.202282S4P518
     [Google Scholar]
  89. A study evaluating the efficacy and safety of giredestrant plus everolimus compared with the physician's choice of endocrine therapy plus everolimus in participants with estrogen receptor-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer).Available from: https://clinicaltrials.gov/study/NCT05306340 2024
  90. MetcalfeC. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes.Canc. Res.201979S4P504
     [Google Scholar]
  91. LimE. A phase Ib study to evaluate the oral selective estrogen receptor degrader GDC-9545 alone or combined with palbociclib in metastatic ER-positive HER2-negative breast cancer.J. Clin. Oncol.202038S15102310.1200/JCO.2020.38.15
     [Google Scholar]
  92. BardiaA. ChandarlapatyS. LindenH.M. UlanerG.A. GosselinA. CottonC.S. CohenP. DoroumianS. PauxG. CelanovicM. PelekanouV. MingJ.E. TernèsN. BouaboulaM. LeeJ.S. BauchetA.L. CamponeM. AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer.Nat. Commun.2022131411610.1038/s41467‑022‑31668‑835840573
     [Google Scholar]
  93. BardiaA. CortesJ. HurvitzS.A. DelalogeS. IwataH. ShaoZ.M. KanagavelD. CohenP. LiuQ. CottonC.S. PelekanouV. O’ShaughnessyJ. AMEERA-5: A randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2– advanced breast cancer.Ther. Adv. Med. Oncol.2022141758835922108395610.1177/1758835922108395635309087
     [Google Scholar]
  94. ShomaliM. ChengJ. SunF. KoundinyaM. GuoZ. HebertA.T. McManusJ. LevitM.N. HoffmannD. CourjaudA. ArrebolaR. CaoH. PollardJ. LeeJ.S. BesretL. CaronA. BangariD.S. AbecassisP.Y. SchioL. AhmadE.Y. HalleyF. TabartM. CertalV. ThompsonF. McCortG. RomméF.B. ChengH. EcheverriaG.C. DebusscheL. BouaboulaM. SAR439859, A novel selective estrogen receptor degrader (SERD), demonstrates effective and broad antitumor activity in wild-type and mutant ER-positive breast cancer models.Mol. Cancer Ther.202120225026210.1158/1535‑7163.MCT‑20‑039033310762
     [Google Scholar]
  95. LindenH.M. Abstract PD8-08: A phase 1/2 study of SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), as monotherapy and in combination with other anti-cancer therapies in postmenopausal women with ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC): AMEERA-1.Canc. Res.202181S4PD808
     [Google Scholar]
  96. TolaneyS.M. ChanA. PetrakovaK. DelalogeS. CamponeM. IwataH. PeddiP.F. KaufmanP.A. KermadecD.E. LiuQ. CohenP. PauxG. WangL. TernèsN. BoitierE. ImS.A. AMEERA-3: Randomized phase II study of amcenestrant (Oral Selective Estrogen Receptor Degrader) versus standard endocrine monotherapy in estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.J. Clin. Oncol.202341244014402410.1200/JCO.22.0274637348019
     [Google Scholar]
  97. CamponeM. BidardF.C. NevenP. WangL. LingB. DongY. PauxG. HeroldC. GiorgiD.U. AMEERA-4: A randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer.Breast Cancer Res.202325114110.1186/s13058‑023‑01740‑237950338
     [Google Scholar]
  98. AndreanoK.J. WardellS.E. BakerJ.G. DesautelsT.K. BaldiR. ChaoC.A. HeetderksK.A. BaeY. XiongR. TonettiD.A. GutgesellL.M. ZhaoJ. SorrentinoJ.A. ThompsonD.A. BisiJ.E. StrumJ.C. ThatcherG.R.J. NorrisJ.D. G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer.Breast Cancer Res. Treat.2020180363564610.1007/s10549‑020‑05575‑932130619
     [Google Scholar]
  99. DeesE.C. AftimosP.G. Oordtv.H. VriesD.E.G.E. NevenP. PegramM.D. IqbalR. BoersJ. XiaoJ. SipesC. LiC. SorrentinoJ.A. MalikR. BeelenA.P. Menke-van derC.W. Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC).Ann. Oncol.201930v121v12210.1093/annonc/mdz242.035
     [Google Scholar]
  100. BeelenA.P. LiC. JarugulaP. GopalakrishnanM. SorrentinoJ.A. WolfgangC.D. JainS. TaoW. Abstract PS17-08: Population pharmacokinetic and exposure-response modeling of the oral selective estrogen receptor degrader, rintodestrant (G1T48), in patients with ER+/HER2- advanced breast cancer.Cancer Res.202181S4PS17-0810.1158/1538‑7445.SABCS20‑PS17‑08
     [Google Scholar]
  101. AftimosP. Rintodestrant (G1T48), an oral selective estrogen receptor degrader, in ER+/HER2–locally advanced or metastatic breast cancer: Updated phase 1 results and dose selection.Menopause202123
     [Google Scholar]
  102. LawsonM. CuretonN. RosS. BashiC.A. UrosevicJ. D’ArcyS. DelpuechO. DuPontM. FisherD.I. GanglE.T. LewisH. TruemanD. WaliN. WilliamsonS.C. MossJ. MontaudonE. DerrienH. MarangoniE. MiragaiaR.J. GagricaS. GutierrezM.P. MossT.A. MaglennonG. SuttonD. PolanskiR. RosenA. CairnsJ. ZhangP. GuixéS.M. SerraV. CritchlowS.E. ScottJ.S. LindemannJ.P.O. BarryS.T. KlinowskaT. MorrowC.J. CarnevalliL.S. The next-generation oral selective estrogen receptor degrader camizestrant (AZD9833) suppresses ER+ breast cancer growth and overcomes endocrine and CDK4/6 inhibitor resistance.Cancer Res.202383233989400410.1158/0008‑5472.CAN‑23‑069437725704
     [Google Scholar]
  103. BairdR. Abstract PS11-05: Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy and in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer.Canc. Res.202181S4PS1105
     [Google Scholar]
  104. Im, S-A.; Hamilton, E.P.; Cussac, A.L.; Baird, R.D.; Ettl, J.; Goetz, M.P.; Iwata, H.; Joy, A.A.; Neven, P.; Haddad, V.; Walding, A.S.; Miralles, M.S.; Bartlett, C.H.; Andr, F. SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease.J. Clin. Oncol.202139S15TPS110110.1200/JCO.2021.39.15
     [Google Scholar]
  105. Bidard, F-C.; Kalinsky, K.; Cristofanilli, M.; Bianchini, G.; Chia, S.; Janni, W.; Ma, C.; Mayer, E.L.; Park, Y.H. Fox, S.; Liu, X.; Walding, A.; Bartlett, C.H.; Turner, N.C. Abstract OT2-11-05: SERENA-6: A Phase III study to assess the efficacy and safety of AZD9833 (camizestrant) compared with aromatase inhibitors when given in combination with palbociclib or abemaciclib in patients with HR+/HER2- metastatic breast cancer with detectable ESR1m who have not experienced disease progression on first-line therapy.Canc. Res.202282S4OT21110.1158/1538‑7445.SABCS21‑OT2‑11‑05
     [Google Scholar]
  106. TurnerN. BartlettH.C. KalinskyK. CristofanilliM. BianchiniG. ChiaS. IwataH. JanniW. MaC.X. MayerE.L. ParkY.H. FoxS. LiuX. McClainS. BidardF.C. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1 -mutant breast cancer during first-line treatment.Future Oncol.202319855957310.2217/fon‑2022‑119637070653
     [Google Scholar]
  107. Jhaveri, K.L.; Jeselsohn, R.; Elgene Lim, E.; Hamilton, E.P.; Yonemori, K.; Beck, J. T.; Kaufman, P.A; Sammons, S.; Bhave, M.A.; Saura, C.; Calvo, E.; Meniawy, T.; Larson, T.; Ma, C.X.; García-Corbacho, J.; Cao, S.; Estrem, S.T.; Milata, J. L.; Nguyen, B.;and Beeram, M. A phase 1a/b trial of imlunestrant (LY3484356), an oral selective estrogen receptor degrader (SERD) in ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Monotherapy results from EMBER.J. Clin. Oncol.20224016 Suppl102110.1200/JCO.2022.40.16_suppl.1021
     [Google Scholar]
  108. JhaveriK.L. LimE. HamiltonE.P. SauraC. MeniawyT. JeselsohnR. BeckJ.T. KaufmanP.A. SammonsS. BandaK. OkeraM. YonemoriK. HarndenK.K. KimS.B. SohnJ. MaC.X. AftimosP.G. WangX.A. YoungS.R.L. BeeramM. A first-in-human phase 1a/b trial of LY3484356, an oral selective estrogen receptor (ER) degrader (SERD) in ER+ advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Results from the EMBER study.J. Clin. Oncol.20213915_suppl105010.1200/JCO.2021.39.15_suppl.1050
     [Google Scholar]
  109. WeirH.M. BradburyR.H. LawsonM. RabowA.A. ButtarD. CallisR.J. CurwenJ.O. Almeidad.C. BallardP. HulseM. DonaldC.S. FeronL.J.L. KaroutchiG. MacFaulP. MossT. NormanR.A. PearsonS.E. TongeM. DaviesG. WalkerG.E. WilsonZ. RowlinsonR. PowellS. SadlerC. RichmondG. LaddB. PazolliE. MazzolaA.M. D’CruzC. SaviD.C. AZD9496: An oral estrogen receptor inhibitor that blocks the growth of ER-positive and ESR1 -mutant breast tumors in preclinical models.Cancer Res.201676113307331810.1158/0008‑5472.CAN‑15‑235727020862
     [Google Scholar]
  110. HamiltonE.P. PatelM.R. ArmstrongA.C. BairdR.D. JhaveriK. HochM. KlinowskaT. LindemannJ.P.O. MorganS.R. SchiavonG. WeirH.M. ImS.A. A first-in-human study of the new oral selective estrogen receptor degrader AZD9496 for ER+/HER2− advanced breast cancer.Clin. Cancer Res.201824153510351810.1158/1078‑0432.CCR‑17‑310229440181
     [Google Scholar]
  111. SamatarA.A. LiJ. HegdeS. HuangP. MaJ. BunkerK. WinklerR. DonateF. SergeevaM. Abstract 4373: Discovery of ZN-c5, a novel potent and oral selective estrogen receptor degrader.Cancer Res.20208016_Supplement437310.1158/1538‑7445.AM2020‑4373
     [Google Scholar]
  112. NeupaneN. BawekS. GurusingheS. GhaffaryE.M. MirmosayyebO. ThapaS. FalksonC. O’ReganR. DhakalA. Oral SERD, a novel endocrine therapy for estrogen receptor-positive breast cancer.Cancers202416361910.3390/cancers1603061938339371
     [Google Scholar]
  113. LiuJ. ZhengS. AkerstromV.L. YuanC. MaY. ZhongQ. ZhangC. ZhangQ. GuoS. MaP. SkripnikovaE.V. BrattonM.R. PannutiA. MieleL. WieseT.E. WangG. Fulvestrant-3 boronic acid (ZB716): An orally bioavailable selective estrogen receptor downregulator (SERD).J. Med. Chem.201659178134814010.1021/acs.jmedchem.6b0075327529700
     [Google Scholar]
  114. PuyangX. FurmanC. ZhengG.Z. WuZ.J. BankaD. AithalK. AgoulnikS. BolducD.M. BuonamiciS. CalebB. DasS. EckleyS. FekkesP. HaoM.H. HartA. HoutmanR. IrwinS. JoshiJ.J. KarrC. KimA. KumarN. KumarP. KuznetsovG. LaiW.G. LarsenN. MackenzieC. MartinL.A. MelchersD. MoriartyA. NguyenT.V. NorrisJ. O’SheaM. PancholiS. PrajapatiS. RajagopalanS. ReynoldsD.J. RimkunasV. RiouxN. RibasR. SiuA. SivakumarS. SubramanianV. ThomasM. VaillancourtF.H. WangJ. WardellS. WickM.J. YaoS. YuL. WarmuthM. SmithP.G. ZhuP. KorpalM. Discovery of selective estrogen receptor covalent antagonists for the treatment of ERαWT and ERαMUT breast cancer.Cancer Discov.2018891176119310.1158/2159‑8290.CD‑17‑122929991605
     [Google Scholar]
  115. FurmanC. PuyangX. ZhangZ. WuZ.J. BankaD. AithalK.B. AlbackerL.A. HaoM.H. IrwinS. KimA. MontesionM. MoriartyA.D. MurugesanK. NguyenT.V. RimkunasV. SahmoudT. WickM.J. YaoS. ZhangX. ZengH. VaillancourtF.H. BolducD.M. LarsenN. ZhengG.Z. PrajapatiS. ZhuP. KorpalM. Covalent ERα antagonist H3B-6545 demonstrates encouraging preclinical activity in therapy-resistant breast cancer.Mol. Cancer Ther.202221689090210.1158/1535‑7163.MCT‑21‑037835642432
     [Google Scholar]
  116. HamiltonE.P. Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.J. Clin. Oncol.2021391018
     [Google Scholar]
  117. CarlosA. Abstract P037: A phase 1/2 dose escalation and expansion study of OP-1250 in adults with advanced and/or metastatic hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancer.Mol Cancer Ther202120S12P037
     [Google Scholar]
  118. ManishP. Abstract P1-17-12: Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer.Cancer Res202282S4P117-12
     [Google Scholar]
  119. ParisianA.D. BarrattS.A. GallagherH.L. OrtegaF.E. PeñaG. SapugayJ. RobelloB. SunR. KulpD. PalanisamyG.S. MylesD.C. KushnerP.J. HarmonC.L. Palazestrant (OP-1250), a complete estrogen receptor antagonist, inhibits wild-type and mutant ER-positive breast cancer models as monotherapy and in combination.Mol. Cancer Ther.202423328530010.1158/1535‑7163.MCT‑23‑035138102750
     [Google Scholar]
  120. XiongR. PatelH.K. GutgesellL.M. ZhaoJ. RiveraD.L. PhamT.N.D. ZhaoH. CarlsonK. MartinT. KatzenellenbogenJ.A. MooreT.W. TonettiD.A. ThatcherG.R.J. Selective human estrogen receptor partial agonists (ShERPAs) for tamoxifen-resistant breast cancer.J. Med. Chem.201659121923710.1021/acs.jmedchem.5b0127626681208
     [Google Scholar]
  121. AbderrahmanB. MaximovP.Y. CurpanR.F. HanspalJ.S. FanP. XiongR. TonettiD.A. ThatcherG.R.J. JordanV.C. Pharmacology and molecular mechanisms of clinically relevant estrogen estetrol and estrogen mimic BMI-135 for the treatment of endocrine-resistant breast cancer.Molecul. Pharmacol.202098436438110.1124/molpharm.120.000054
     [Google Scholar]
  122. PatelR. KleinP. TierstenA. SparanoJ.A. An emerging generation of endocrine therapies in breast cancer: A clinical perspective.NPJ Breast Canc.2023912010.1038/s41523‑023‑00523‑437019913
     [Google Scholar]
  123. DouganD.A. MicevskiD. TruscottK.N. The N-end rule pathway: From recognition by N-recognins, to destruction by AAA+proteases.Biochim. Biophys. Acta Mol. Cell Res.201218231839110.1016/j.bbamcr.2011.07.00221781991
     [Google Scholar]
  124. Flanagan, J.J.; Qian, Y.; Gough, S.M.; Andreoli, M.; Bookbinder, M.; Cadelina, G.; Bradley, J.; Rousseau, E.; Willard, R.; Pizzano, J.; Crews, C.M.; Crew, A.P.; Taylor, I.; Houston, J. ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR, Cancer Res. 2019794 Suppl10.1158/1538‑7445.SABCS18‑P5‑04‑18
     [Google Scholar]
  125. WangZ. CheS. YuZ. PROTAC: Novel degradable approach for different targets to treat breast cancer.Eur. J. Pharm. Sci.202419810679310.1016/j.ejps.2024.10679338740076
     [Google Scholar]
  126. KaurR. ChaudharyG. KaurA. SinghP. LongowalG.D. SapkaleG.P. AroraS. PROTACs: A hope for breast cancer patients?Anticancer. Agents Med. Chem.202222340641710.2174/187152062166621030810032733687888
     [Google Scholar]
  127. RoyceM. BachelotT. VillanuevaC. ÖzgürogluM. AzevedoS.J. CruzF.M. DebledM. HeggR. ToyamaT. FalksonC. JeongJ. SrimuninnimitV. GradisharW.J. ArceC. RidolfiA. LinC. CardosoF. Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer.JAMA Oncol.20184797798410.1001/jamaoncol.2018.006029566104
     [Google Scholar]
  128. SafraT. KaufmanB. KadouriL. BaruchE.B.N. RyvoL. NisenbaumB. EvronE. YerushalmiR. Everolimus plus letrozole for treatment of patients with HR+, HER2- advanced breast cancer progressing on endocrine therapy: An open-label, phase II trial.Clin. Breast Cancer2018182e197e20310.1016/j.clbc.2017.09.00429097108
     [Google Scholar]
  129. PuD. XuD. WuY. ChenH. ShiG. FengD. ZhangM. LiuZ. LiJ. Efficacy of CDK4/6 inhibitors combined with endocrine therapy in HR+/HER2− breast cancer: An umbrella review.J. Cancer Res. Clin. Oncol.202415011610.1007/s00432‑023‑05516‑138240835
     [Google Scholar]
  130. GarbánM.D.C. DengG. AnduixC.B. GarciaA.J. XingY. ChenH.W. LauC.G. HamiltonN. JungM.E. PietrasR.J. Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy.J. Steroid Biochem. Mol. Biol.201919310541510.1016/j.jsbmb.2019.10541531226312
     [Google Scholar]
  131. WangY. MindenA. Current molecular combination therapies used for the treatment of breast cancer.Int. J. Mol. Sci.202223191104610.3390/ijms23191104636232349
     [Google Scholar]
  132. KiyotaniK. MushirodaT. NakamuraY. ZembutsuH. Pharmacogenomics of tamoxifen: Roles of drug metabolizing enzymes and transporters.Drug Metab. Pharmacokinet.201227112213110.2133/dmpk.DMPK‑11‑RV‑08422041137
     [Google Scholar]
  133. Villiersd.T.J. Bazedoxifene: A novel selective estrogen receptor modulator for postmenopausal osteoporosis.Climacteric201013321021810.3109/1369713090356854220184423
     [Google Scholar]
  134. BihaniT. PatelH.K. ArltH. TaoN. JiangH. BrownJ.L. PurandareD.M. HattersleyG. GarnerF. Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), has antitumor activity in multiple ER+ breast cancer patient-derived xenograft models.Clin. Cancer Res.201723164793480410.1158/1078‑0432.CCR‑16‑256128473534
     [Google Scholar]
  135. MetcalfeC. Abstract P5-04-07: GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes.Cancer Res201979S4P504-07
     [Google Scholar]
  136. FructuosoS.A.I. Everolimus: An update on the mechanism of action, pharmacokinetics and recent clinical trials.Expert Opin. Drug Metab. Toxicol.20084680781910.1517/17425255.4.6.80718611120
     [Google Scholar]
  137. BowlesH.J. ClarkeK.L. Palbociclib: A new option for front-line treatment of metastatic, hormone receptor-positive, HER2-negative breast cancer.J. Adv. Pract. Oncol.20156657758127648347
     [Google Scholar]
  138. AhmadE.Y. TabartM. HalleyF. CertalV. ThompsonF. RomméF.B. LeleuG.F. MullerC. BrolloM. FabienL. LoyauV. BertinL. RichepinP. PilorgeF. DesmazeauP. GirardetC. BeccariS. LouboutinA. LebourgG. RouxL.J. TerrierC. ValléeF. SteierV. MathieuM. RakA. AbecassisP.Y. VicatP. BenardT. BouaboulaM. SunF. ShomaliM. HebertA. LevitM. ChengH. CourjaudA. GinestyC. PerraultC. EcheverriaG.C. McCortG. SchioL. Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3 S )-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7 H -benzo[7]annulene-2-carboxylic acid (SAR439859), a potent and selective estrogen receptor degrader (SERD) for the treatment of estrogen-receptor-positive breast cancer.J. Med. Chem.202063251252810.1021/acs.jmedchem.9b0129331721572
     [Google Scholar]
  139. DudekA.Z. LiuL.C. FischerJ.H. WileyE.L. SachdevJ.C. BleekerJ. HurleyR.W. TonettiD.A. ThatcherG.R.J. VenutiR.P. O’ReganR.M. Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine and CDK4/6 inhibitor therapy.Breast Cancer Res. Treat.2020183361762710.1007/s10549‑020‑05787‑z32696319
     [Google Scholar]
  140. ScottJ.S. MossT.A. BalazsA. BarlaamB. BreedJ. CarbajoR.J. ChiarparinE. DaveyP.R.J. DelpuechO. FawellS. FisherD.I. GagricaS. GanglE.T. GrebeT. GreenwoodR.D. HandeS. MokdadH.H. HerlihyK. HughesS. HuntT.A. HuynhH. JanbonS.L.M. JohnsonT. KavanaghS. KlinowskaT. LawsonM. ListerA.S. MardenS. McGinnityD.F. MorrowC.J. NissinkJ.W.M. O’DonovanD.H. PengB. PolanskiR. SteadD.S. StokesS. ThakurK. ThronerS.R. TuckerM.J. VarnesJ. WangH. WilsonD.M. WuD. WuY. YangB. YangW. Discovery of AZD9833, a potent and orally bioavailable selective estrogen receptor degrader and antagonist.J. Med. Chem.20206323145301455910.1021/acs.jmedchem.0c0116332910656
     [Google Scholar]
  141. CairnsJ. IngleJ.N. KalariK.R. GoetzM.P. WeinshilboumR.M. GaoH. LiH. BariM.G. WangL. Anastrozole regulates fatty acid synthase in breast cancer.Mol. Cancer Ther.202221120621610.1158/1535‑7163.MCT‑21‑050934667110
     [Google Scholar]
  142. GossP.E. TyeL.M. Anastrozole: A new selective nonsteroidal aromatase inhibitor.Oncology19971111169717039394367
     [Google Scholar]
  143. AhangariF. BeckerC. FosterD.G. ChioccioliM. NelsonM. BekeK. WangX. JustetA. AdamsT. ReadheadB. MeadorC. CorrellK. LiliL.N. RoybalH.M. RoseK.A. DingS. BarnthalerT. BrionesN. DeIuliisG. SchuppJ.C. LiQ. OmoteN. AschnerY. SharmaL. KopfK.W. MagnussonB. HicksR. BackmarkA. CruzD.C.S. RosasI. CousensL.P. DudleyJ.T. KaminskiN. DowneyG.P. Saracatinib, a selective Src kinase inhibitor, blocks fibrotic responses in preclinical models of pulmonary fibrosis.Am. J. Respir. Crit. Care Med.2022206121463147910.1164/rccm.202010‑3832OC35998281
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673345472250301052255
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Analysis of the Main Directions in the Development of Mono and Combination Pharmacotherapy Acting on Hormonal Signaling Pathways of Breast Cancer According to the FDA Databases and Clinicaltrials.gov
Curr. Med. Chem. 32, 8075 (2025); https://doi.org/10.2174/0109298673345472250301052255
/content/journals/cmc/10.2174/0109298673345472250301052255
/content/journals/cmc/10.2174/0109298673345472250301052255
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  • Article Type:     Review Article
Keyword(s): breast cancer; endocrine therapy; estrogen receptors; Hormonal signaling pathways; hormone-dependent tumors; monotherapeutic agents

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