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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Rajwinder Kaur, Gaurav Chaudhary, Amritpal Kaur, Pargat Singh, Gagan Deep Longowal, Gayatri P. Sapkale and Sandeep Arora*

DOI: 10.2174/1871520621666210308100327

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PROTACs: A Hope for Breast Cancer Patients?

Page: [406 - 417] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Background: Breast Cancer (BC) is the most widely occurring disease in women. A massive number of women are diagnosed with breast cancer, and many lose their lives every year. Cancer is the leading cause of death worldwide, posing a formidable challenge to the current medication difficulties.

Objectives: The main objective of this study is to examine and explore novel therapy (PROTAC) and its effectiveness against breast cancer.

Methods: The literature search was conducted across Medline, Cochrane, ScienceDirect, Wiley Online, Google Scholar, PubMed, and Bentham Sciences from 2001 to 2020. The articles collected were screened, segregated, and selected papers were included for writing the review article.

Results and Conclusion: A novel innovation emerged around two decades ago that has great potential to overcome the limitations and provide future direction for the treatment of many diseases, which has presently not many therapeutic options available and are regarded as incurable with traditional techniques. That innovation is called PROTAC (Proteolysis Targeting Chimera), which can efficaciously ubiquitinate and debase cancer, encouraging proteins through noncovalent interaction. PROTACs constituted of two active regions isolated by a linker are equipped for eliminating explicit undesirable protein. It is empowering greater sensitivity to "drugresistant targets" and a more prominent opportunity to influence non-enzymatic function. PROTACs have been demonstrated to show better target selectivity contrasted with traditional small-molecule inhibitors. So far, the most investigation into PROTACs mainly concentrated on cancer treatment applications, including breast cancer. The treatment of different ailments may benefit the patients from this blossoming innovation.

Keywords: Breast cancer, novel therapy, protein degradation, PROTACs, ER-PROTAC, BET-PROTAC, BRD4-degrader.

Graphical Abstract

[1]
Waks, A.G.; Winer, E.P. Breast cancer treatment: a review. JAMA, 2019, 321(3), 288-300.
[http://dx.doi.org/10.1001/jama.2018.19323] [PMID: 30667505]
[2]
Alarming facts about breast cancer in India.. https://www.oncostem.com/blog/alarming-facts-about-breast-cancer-in-india[04/09/2020]; 2020.
[3]
Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018.. https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.iarc.fr/wp-content/uploads/2018/09/pr263_E.pdf&ved=2ahUKEwi4nM_SxpDsAhXCzDgGHTOLDB4QFjAEegQICRAE&usg=AOvVaw2gBxGkWzYIgXuZdJz_TY43&cshid=1601458186604[04/09/2020];2020.
[4]
Breast cancer. World health organization,. https://www.who.int/cancer/prevention/diagnosis-screening/breast-cancer/en/[04/09/2020];2020.
[5]
Latest Statistics of Breast Cancer in India 2020 . https://www. breastcancerindia.net/statistics/latest_statistics_breast_cancer_india.html[04/09/2020];2020.
[6]
U.S. Breast Cancer Statistics. https://www.breastcancer.org/symptoms/understand_bc/statistics [04/09/2020]; 2020.
[7]
Cancer - Statistics & Facts. . https://www.statista.com/topics/1192/cancer-in-the-us/[04/09/2020]; 2020.
[8]
Ginsburg, O.; Yip, C.H.; Brooks, A.; Cabanes, A.; Caleffi, M.; Dunstan Yataco, J.A.; Gyawali, B.; McCormack, V.; McLaughlin de Anderson, M.; Mehrotra, R.; Mohar, A.; Murillo, R.; Pace, L.E.; Paskett, E.D.; Romanoff, A.; Rositch, A.F.; Scheel, J.R.; Schneidman, M.; Unger-Saldaña, K.; Vanderpuye, V.; Wu, T.Y.; Yuma, S.; Dvaladze, A.; Duggan, C.; Anderson, B.O. Breast cancer early detection: a phased approach to implementation. Cancer, 2020, 126(Suppl. 10), 2379-2393.
[http://dx.doi.org/10.1002/cncr.32887] [PMID: 32348566]
[9]
Sakamoto, K.M. Chimeric molecules to target proteins for ubiquitination and degradation. Methods Enzymol., 2005, 399, 833-847.
[http://dx.doi.org/10.1016/S0076-6879(05)99054-X] [PMID: 16338398]
[10]
Zhao, Q.; Lan, T.; Su, S.; Rao, Y. Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule. Chem. Commun. (Camb.), 2019, 55(3), 369-372.
[http://dx.doi.org/10.1039/C8CC07813K] [PMID: 30540295]
[11]
Sakamoto, K.M. Protacs for treatment of cancer. Pediatr. Res., 2010, 67(5), 505-508.
[http://dx.doi.org/10.1203/PDR.0b013e3181d35017] [PMID: 20075761]
[12]
Farnaby, W.; Koegl, M.; Roy, M.J.; Whitworth, C.; Diers, E.; Trainor, N.; Zollman, D.; Steurer, S.; Karolyi-Oezguer, J.; Riedmueller, C.; Gmaschitz, T.; Wachter, J.; Dank, C.; Galant, M.; Sharps, B.; Rumpel, K.; Traxler, E.; Gerstberger, T.; Schnitzer, R.; Petermann, O.; Greb, P.; Weinstabl, H.; Bader, G.; Zoephel, A.; Weiss-Puxbaum, A.; Ehrenhöfer-Wölfer, K.; Wöhrle, S.; Boehmelt, G.; Rinnenthal, J.; Arnhof, H.; Wiechens, N.; Wu, M.Y.; Owen-Hughes, T.; Ettmayer, P.; Pearson, M.; McConnell, D.B.; Ciulli, A. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Nat. Chem. Biol., 2019, 15(7), 672-680.
[http://dx.doi.org/10.1038/s41589-019-0294-6] [PMID: 31178587]
[13]
Sun, X.; Rao, Y. PROTACs as potential therapeutic agents for cancer drug resistance. Biochemistry, 2020, 59(3), 240-249.
[http://dx.doi.org/10.1021/acs.biochem.9b00848] [PMID: 31661257]
[14]
Ocaña, A.; Pandiella, A. Proteolysis targeting chimeras (PROTACs) in cancer therapy. J. Exp. Clin. Cancer Res., 2020, 39(1), 189.
[http://dx.doi.org/10.1186/s13046-020-01672-1] [PMID: 32933565]
[15]
Du, M.; Wang, G.; Ismail, T.M. Proteolysis-targeting chimera (PROTAC) compounds to degrade S100A4 and inhibit breast cancer metastasis. Ann. Oncol., 2018, 29(suppl_9), mdy428-020.,
[16]
Wan, Y.; Yan, C.; Gao, H.; Liu, T. Small-molecule PROTACs: novel agents for cancer therapy. Future Med. Chem., 2020, 12(10), 915-938.
[http://dx.doi.org/10.4155/fmc-2019-0340] [PMID: 32270707]
[17]
Konstantinidou, M.; Li, J.; Zhang, B.; Wang, Z.; Shaabani, S.; Ter Brake, F.; Essa, K.; Dömling, A. PROTACs- a game-changing technology. Expert Opin. Drug Discov., 2019, 14(12), 1255-1268.
[http://dx.doi.org/10.1080/17460441.2019.1659242] [PMID: 31538491]
[18]
Sakamoto, K.M.; Kim, K.B.; Verma, R.; Ransick, A.; Stein, B.; Crews, C.M.; Deshaies, R.J. Development of PROTACs to target cancer-promoting proteins for ubiquitination and degradation. Mol. Cell. Proteomics, 2003, 2(12), 1350-1358.
[http://dx.doi.org/10.1074/mcp.T300009-MCP200] [PMID: 14525958]
[19]
Zhou, X.; Dong, R.; Zhang, J.Y.; Zheng, X.; Sun, L.P. PROTAC: a promising technology for cancer treatment. Eur. J. Med. Chem., 2020, 203112539
[http://dx.doi.org/10.1016/j.ejmech.2020.112539] [PMID: 32698111]
[20]
Cromm, P.M.; Crews, C.M. Targeted protein degradation: from chemical biology to drug discovery. Cell Chem. Biol., 2017, 24(9), 1181-1190.
[http://dx.doi.org/10.1016/j.chembiol.2017.05.024] [PMID: 28648379]
[21]
Hu, J.; Hu, B.; Wang, M.; Xu, F.; Miao, B.; Yang, C.Y.; Wang, M.; Liu, Z.; Hayes, D.F.; Chinnaswamy, K.; Delproposto, J.; Stuckey, J.; Wang, S. Discovery of ERD-308 as a highly potent proteolysis targeting chimera (PROTAC) degrader of Estrogen Receptor (ER). J. Med. Chem., 2019, 62(3), 1420-1442.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01572] [PMID: 30990042]
[22]
Guo, J.; Liu, J.; Wei, W. Degrading proteins in animals: “PROTAC”tion goes in vivo. Cell Res., 2019, 29(3), 179-180.
[http://dx.doi.org/10.1038/s41422-019-0144-9] [PMID: 30770868]
[23]
Chopra, R.; Sadok, A.; Collins, I. A critical evaluation of the approaches to targeted protein degradation for drug discovery. Drug Discov. Today. Technol., 2019, 31, 5-13.
[http://dx.doi.org/10.1016/j.ddtec.2019.02.002] [PMID: 31200859]
[24]
Wang, Y.; Jiang, X.; Feng, F.; Liu, W.; Sun, H. Degradation of proteins by PROTACs and other strategies. Acta Pharm. Sin. B, 2020, 10(2), 207-238.
[http://dx.doi.org/10.1016/j.apsb.2019.08.001] [PMID: 32082969]
[25]
Schapira, M.; Calabrese, M.F.; Bullock, A.N.; Crews, C.M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov., 2019, 18(12), 949-963.
[http://dx.doi.org/10.1038/s41573-019-0047-y] [PMID: 31666732]
[26]
Pohl, C.; Dikic, I. Cellular quality control by the ubiquitin-proteasome system and autophagy. Science, 2019, 366(6467), 818-822.
[http://dx.doi.org/10.1126/science.aax3769] [PMID: 31727826]
[27]
Ottis, P.; Toure, M.; Cromm, P.M.; Ko, E.; Gustafson, J.L.; Crews, C.M. Assessing different E3 ligases for small molecule induced protein ubiquitination and degradation. ACS Chem. Biol., 2017, 12(10), 2570-2578.
[http://dx.doi.org/10.1021/acschembio.7b00485] [PMID: 28767222]
[28]
Carmony, K.C.; Kim, K.B. PROTAC-induced proteolytic targeting.Ubiquitin Family Modifiers and the Proteasome. Methods in molecular biology (Methods and Protocols); Dohmen, R.; Scheffner, M., Eds.; Springer: Germany, 2012, Vol. 832, pp. 627-638.
[http://dx.doi.org/10.1007/978-1-61779-474-2_44]
[29]
Tan, L.; Gray, N.S. When kinases meet PROTACs. Chin. J. Chem., 2018, 36(10), 971-977.
[http://dx.doi.org/10.1002/cjoc.201800293]
[30]
Burslem, G.M.; Crews, C.M. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell, 2020, 181(1), 102-114.
[http://dx.doi.org/10.1016/j.cell.2019.11.031] [PMID: 31955850]
[31]
Moon, S.; Lee, B.H. Chemically induced cellular proteolysis: an emerging therapeutic strategy for undruggable targets. Mol. Cells, 2018, 41(11), 933-942.
[PMID: 30486612]
[32]
Chen, Y.; Jin, J. The application of ubiquitin ligases in the PROTAC drug design. Acta Biochim. Biophys. Sin. (Shanghai), 2020, 52(7), 776-790.
[http://dx.doi.org/10.1093/abbs/gmaa053] [PMID: 32506133]
[33]
Khan, S.; He, Y.; Zhang, X.; Yuan, Y.; Pu, S.; Kong, Q.; Zheng, G.; Zhou, D. PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics. Oncogene, 2020, 39, 4909-4924.
[34]
Edmondson, S.D.; Yang, B.; Fallan, C. Proteolysis targeting chimeras (PROTACs) in ‘beyond rule-of-five’ chemical space: recent progress and future challenges. Bioorg. Med. Chem. Lett., 2019, 29(13), 1555-1564.
[http://dx.doi.org/10.1016/j.bmcl.2019.04.030] [PMID: 31047748]
[35]
An, S.; Fu, L. Small-molecule PROTACs: an emerging and promising approach for the development of targeted therapy drugs. EBioMedicine, 2018, 36, 553-562.
[http://dx.doi.org/10.1016/j.ebiom.2018.09.005] [PMID: 30224312]
[36]
Scheepstra, M.; Hekking, K.F.W.; van Hijfte, L.; Folmer, R.H.A. Bivalent ligands for protein degradation in drug discovery. Comput. Struct. Biotechnol. J., 2019, 17, 160-176.
[http://dx.doi.org/10.1016/j.csbj.2019.01.006] [PMID: 30788082]
[37]
Moreau, K.; Coen, M.; Zhang, A.X.; Pachl, F.; Castaldi, M.P.; Dahl, G.; Boyd, H.; Scott, C.; Newham, P. Proteolysis-targeting chimeras in drug development: a safety perspective. Br. J. Pharmacol., 2020, 177(8), 1709-1718.
[http://dx.doi.org/10.1111/bph.15014] [PMID: 32022252]
[38]
Zhang, Y.; Loh, C.; Chen, J.; Mainolfi, N. Targeted protein degradation mechanisms. Drug Discov. Today. Technol., 2019, 31, 53-60.
[http://dx.doi.org/10.1016/j.ddtec.2019.01.001] [PMID: 31200860]
[39]
Xi, M.; Chen, Y.; Yang, H.; Xu, H.; Du, K.; Wu, C.; Xu, Y.; Deng, L.; Luo, X.; Yu, L.; Wu, Y.; Gao, X.; Cai, T.; Chen, B.; Shen, R.; Sun, H. Small molecule PROTACs in targeted therapy: an emerging strategy to induce protein degradation. Eur. J. Med. Chem., 2019, 174, 159-180.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.036] [PMID: 31035238]
[40]
Chamberlain, P.P.; Hamann, L.G. Development of targeted protein degradation therapeutics. Nat. Chem. Biol., 2019, 15(10), 937-944.
[http://dx.doi.org/10.1038/s41589-019-0362-y] [PMID: 31527835]
[41]
Liu, J.; Ma, J.; Liu, Y.; Xia, J.; Li, Y.; Wang, Z.P.; Wei, W. PROTACs: a novel strategy for cancer therapy.Seminars in Cancer Biology; Academic Press: USA, 2020.
[http://dx.doi.org/10.1016/j.semcancer.2020.02.006]
[42]
Gu, S.; Cui, D.; Chen, X.; Xiong, X.; Zhao, Y. PROTACs: an emerging targeting technique for protein degradation in drug discovery. BioEssays, 2018, 40(4)e1700247
[http://dx.doi.org/10.1002/bies.201700247] [PMID: 29473971]
[43]
Ohoka, N.; Shibata, N.; Hattori, T.; Naito, M. Protein knockdown technology: application of ubiquitin ligase to cancer therapy. Curr. Cancer Drug Targets, 2016, 16(2), 136-146.
[http://dx.doi.org/10.2174/1568009616666151112122502] [PMID: 26560118]
[44]
Naito, M.; Ohoka, N.; Shibata, N. SNIPERs-Hijacking IAP activity to induce protein degradation. Drug Discov. Today. Technol., 2019, 31, 35-42.
[http://dx.doi.org/10.1016/j.ddtec.2018.12.002] [PMID: 31200857]
[45]
Xue, G.; Wang, K.; Zhou, D.; Zhong, H.; Pan, Z. Light-induced protein degradation with photocaged PROTACs. J. Am. Chem. Soc., 2019, 141(46), 18370-18374.
[http://dx.doi.org/10.1021/jacs.9b06422] [PMID: 31566962]
[46]
Ohoka, N.; Okuhira, K.; Ito, M.; Nagai, K.; Shibata, N.; Hattori, T.; Ujikawa, O.; Shimokawa, K.; Sano, O.; Koyama, R.; Fujita, H.; Teratani, M.; Matsumoto, H.; Imaeda, Y.; Nara, H.; Cho, N.; Naito, M. In vivo knockdown of pathogenic proteins via specific and nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent protein erasers (SNIPERs). J. Biol. Chem., 2017, 292(11), 4556-4570.
[http://dx.doi.org/10.1074/jbc.M116.768853] [PMID: 28154167]
[47]
Wei, M.; Zhao, R.; Cao, Y.; Wei, Y.; Li, M.; Dong, Z.; Liu, Y.; Ruan, H.; Li, Y.; Cao, S.; Tang, Z.; Zhou, Y.; Song, W.; Wang, Y.; Wang, J.; Yang, G.; Yang, C. First orally bioavailable prodrug of proteolysis targeting chimera (PROTAC) degrades cyclin-dependent kinases 2/4/6 in vivo. Eur. J. Med. Chem., 2021, 209112903
[http://dx.doi.org/10.1016/j.ejmech.2020.112903] [PMID: 33256948]
[48]
Zhou, F.; Chen, L.; Cao, C.; Yu, J.; Luo, X.; Zhou, P.; Zhao, L.; Du, W.; Cheng, J.; Xie, Y.; Chen, Y. Development of selective mono or dual PROTAC degrader probe of CDK isoforms. Eur. J. Med. Chem., 2020, 187111952
[http://dx.doi.org/10.1016/j.ejmech.2019.111952] [PMID: 31846828]
[49]
Nalawansha, D.A.; Crews, C.M. PROTACs: an emerging therapeutic modality in precision medicine. Cell Chem. Boil.,, 2020, 27(8), 998-1014.
[50]
Churcher, I. PROTAC-induced protein degradation in drug discovery: breaking the rules or just making new ones? J. Med. Chem., 2018, 61(2), 444-452.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01272] [PMID: 29144739]
[51]
Pettersson, M.; Crews, C.M. PROteolysis TArgeting Chimeras (PROTACs)-past, present and future. Drug Discov. Today. Technol., 2019, 31, 15-27.
[http://dx.doi.org/10.1016/j.ddtec.2019.01.002] [PMID: 31200855]
[52]
Li, X.; Song, Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J. Hematol. Oncol., 2020, 13(1), 50.
[http://dx.doi.org/10.1186/s13045-020-00885-3] [PMID: 32404196]
[53]
Pei, H.; Peng, Y.; Zhao, Q.; Chen, Y. Small molecule PROTACs: an emerging technology for targeted therapy in drug discovery. RSC Advances, 2019, 9(30), 16967-16976.
[http://dx.doi.org/10.1039/C9RA03423D]
[54]
Fang, Y.; Liao, G.; Yu, B. Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives. Acta Pharm. Sin. B, 2020, 10(7), 1253-1278.
[http://dx.doi.org/10.1016/j.apsb.2020.01.003] [PMID: 32874827]
[55]
Li, Y.; Yang, J.; Aguilar, A.; McEachern, D.; Przybranowski, S.; Liu, L.; Yang, C.Y.; Wang, M.; Han, X.; Wang, S. Discovery of MD-224 as a first-in-class, highly potent and efficacious PROTAC MDM2 degrader capable of achieving complete and durable tumor regression. J. Med. Chem., 2019, 62(2), 448.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00909] [PMID: 30525597]
[56]
ClinicalTrial.gov. Trial of ARV-110 in Patients with Metastatic Castration- Resistant Prostate Cancer (mCRPC),. https://clinicaltrials.gov/ct2/show/NCT03888612 [07/10/2020]; 2020.
[57]
ClinicalTrial.gov. Clinical Trial of ARV-471 in Patients with ER+/HER2- Locally Advanced or Metastatic Breast Cancer (mBC),. https://clinicaltrials.gov/ct2/show/NCT04072952 [07/10/2020];2020.
[58]
Maneiro, M.A.; Forte, N.; Shchepinova, M.M.; Kounde, C.S.; Chudasama, V.; Baker, J.R.; Tate, E.W. Antibody-PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4. ACS Chem. Biol., 2020, 15(6), 1306-1312.
[http://dx.doi.org/10.1021/acschembio.0c00285] [PMID: 32338867]
[59]
Paiva, S.L.; Crews, C.M. Targeted protein degradation: elements of PROTAC design. Curr. Opin. Chem. Biol., 2019, 50, 111-119.
[http://dx.doi.org/10.1016/j.cbpa.2019.02.022] [PMID: 31004963]
[60]
Zou, Y.; Ma, D.; Wang, Y. The PROTAC technology in drug development. Cell Biochem. Funct., 2019, 37(1), 21-30.
[http://dx.doi.org/10.1002/cbf.3369] [PMID: 30604499]
[61]
Jiang, Y.; Deng, Q.; Zhao, H.; Xie, M.; Chen, L.; Yin, F.; Qin, X.; Zheng, W.; Zhao, Y.; Li, Z. Development of stabilized peptide-based PROTACs against estrogen receptor α. ACS Chem. Biol., 2018, 13(3), 628-635.
[http://dx.doi.org/10.1021/acschembio.7b00985] [PMID: 29271628]
[62]
Zhang, D.; Baek, S.H.; Ho, A.; Kim, K. Degradation of target protein in living cells by small-molecule proteolysis inducer. Bioorg. Med. Chem. Lett., 2004, 14(3), 645-648.
[http://dx.doi.org/10.1016/j.bmcl.2003.11.042] [PMID: 14741260]
[63]
Donoghue, C.; Cubillos-Rojas, M.; Gutierrez-Prat, N.; Sanchez-Zarzalejo, C.; Verdaguer, X.; Riera, A.; Nebreda, A.R. Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation. Eur. J. Med. Chem., 2020, 201112451
[http://dx.doi.org/10.1016/j.ejmech.2020.112451] [PMID: 32634680]
[64]
Gao, H.; Sun, X.; Rao, Y. PROTAC technology: opportunities and challenges. ACS Med. Chem. Lett., 2020, 11(3), 237-240.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00597] [PMID: 32184950]
[65]
Sun, X.; Gao, H.; Yang, Y.; He, M.; Wu, Y.; Song, Y.; Tong, Y.; Rao, Y. PROTACs: great opportunities for academia and industry. Signal Trans. Target. Ther., 2019, 4(1), 64.
[http://dx.doi.org/10.1038/s41392-019-0101-6] [PMID: 31885879]
[66]
Sahni, J.M.; Keri, R.A. Targeting bromodomain and extraterminal proteins in breast cancer. Pharmacol. Res., 2018, 129, 156-176.
[http://dx.doi.org/10.1016/j.phrs.2017.11.015] [PMID: 29154989]
[67]
Kwan, M.L.; Kushi, L.H.; Weltzien, E.; Maring, B.; Kutner, S.E.; Fulton, R.S.; Lee, M.M.; Ambrosone, C.B.; Caan, B.J. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res., 2009, 11(3), R31.
[http://dx.doi.org/10.1186/bcr2261] [PMID: 19463150]
[68]
Onitilo, 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(1-2), 4-13.
[http://dx.doi.org/10.3121/cmr.2008.825] [PMID: 19574486]
[69]
Mehdi, I.; Monem, A.A.; Al Bahrani, B.; Ramadhan, F.A. Breast cancer molecular subtypes in oman: correlation with age, histology, and stage distribution - analysis of 542 cases. Gulf J. Oncolog., 2014, 1(15), 38-48.
[PMID: 24610287]
[70]
Taherian-Fard, A.; Srihari, S.; Ragan, M.A. Breast cancer classification: linking molecular mechanisms to disease prognosis. Brief. Bioinform., 2015, 16(3), 461-474.
[http://dx.doi.org/10.1093/bib/bbu020] [PMID: 24950687]
[71]
de Ronde, J.J.; Hannemann, J.; Halfwerk, H.; Mulder, L.; Straver, M.E.; Vrancken Peeters, M.J.; Wesseling, J.; van de Vijver, M.; Wessels, L.F.; Rodenhuis, S. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Res. Treat., 2010, 119(1), 119-126.
[http://dx.doi.org/10.1007/s10549-009-0499-6] [PMID: 19669409]
[72]
https://www.breastcancer.org/symptoms/types/molecular-subtypes2020.
[73]
Zhao, L.; Han, X.; Lu, J.; McEachern, D.; Wang, S. A highly potent PROTAC Androgen Receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo. Neoplasia, 2020, 22(10), 522-532.
[http://dx.doi.org/10.1016/j.neo.2020.07.002] [PMID: 32928363]
[74]
Wilcken, N.; Hornbuckle, J.; Ghersi, D. Chemotherapy alone versus endocrine therapy alone for metastatic breast cancer. Cochrane Database Syst. Rev., 2003, 2.
[http://dx.doi.org/10.1002/14651858.CD002747]
[75]
Hanker, A.B.; Sudhan, D.R.; Arteaga, C.L. overcoming endocrine resistance in breast cancer. Cancer Cell, 2020, 37(4), 496-513.
[http://dx.doi.org/10.1016/j.ccell.2020.03.009] [PMID: 32289273]
[76]
Shagufta; Ahmad, I.; Mathew, S.; Rahman, S. Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer. RSC Med. Chem., 2020, 11(4), 438-454.
[http://dx.doi.org/10.1039/C9MD00570F] [PMID: 33479648]
[77]
Lumachi, F.; Brunello, A.; Maruzzo, M.; Basso, U.; Basso, S.M. Treatment of estrogen receptor-positive breast cancer. Curr. Med. Chem., 2013, 20(5), 596-604.
[http://dx.doi.org/10.2174/092986713804999303] [PMID: 23278394]
[78]
Gibson, L.; Lawrence, D.; Dawson, C.; Bliss, J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst. Rev., 2009, 4.
[http://dx.doi.org/10.1002/14651858.CD003370.pub3]
[79]
Lee, C.I.; Goodwin, A.; Wilcken, N. Fulvestrant for hormone‐sensitive metastatic breast cancer. Cochrane Database Syst. Rev., 2017, 1.
[http://dx.doi.org/10.1002/14651858.CD011093.pub2]
[80]
Balduzzi, S.; Mantarro, S.; Guarneri, V.; Tagliabue, L.; Pistotti, V.; Moja, L.; D’Amico, R. Trastuzumab‐containing regimens for metastatic breast cancer. Cochrane Database Syst. Rev., 2014, 6.
[http://dx.doi.org/10.1002/14651858.CD006242.pub2]
[81]
Qin, J.J.; Yan, L.; Zhang, J.; Zhang, W.D. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J. Exp. Clin. Cancer Res., 2019, 38(1), 195.
[http://dx.doi.org/10.1186/s13046-019-1206-z] [PMID: 31088482]
[82]
del Mar Noblejas-López, M.; Nieto-Jimenez, C.; Burgos, M.; Gómez-Juárez, M.; Montero, J.C.; Esparís-Ogando, A.; Pandiella, A.; Galán-Moya, E.M.; Ocaña, A. Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer. J. Exp. Clin. Cancer Res., 2019, 38(1), 1-9.
[PMID: 30606223]
[83]
Bondeson, D.P.; Crews, C.M. Targeted protein degradation by small molecules. Annu. Rev. Pharmacol. Toxicol., 2017, 57, 107-123.
[http://dx.doi.org/10.1146/annurev-pharmtox-010715-103507] [PMID: 27732798]
[84]
Bai, L.; Zhou, B.; Yang, C.Y.; Ji, J.; McEachern, D.; Przybranowski, S.; Jiang, H.; Hu, J.; Xu, F.; Zhao, Y.; Liu, L.; Fernandez-Salas, E.; Xu, J.; Dou, Y.; Wen, B.; Sun, D.; Meagher, J.; Stuckey, J.; Hayes, D.F.; Li, S.; Ellis, M.J.; Wang, S. Targeted degradation of BET proteins in triple-negative breast cancer. Cancer Res., 2017, 77(9), 2476-2487.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-2622] [PMID: 28209615]
[85]
Itoh, Y.; Kitaguchi, R.; Ishikawa, M.; Naito, M.; Hashimoto, Y. Design, synthesis and biological evaluation of nuclear receptor-degradation inducers. Bioorg. Med. Chem., 2011, 19(22), 6768-6778.
[http://dx.doi.org/10.1016/j.bmc.2011.09.041] [PMID: 22014751]
[86]
Mukhamejanova, Z.; Tong, Y.; Xiang, Q.; Xu, F.; Pang, J. Recent advances in the design and development of anticancer molecules based on PROTAC technology. Curr. Med. Chem., 2021, 28(7), 1304-1327.
[http://dx.doi.org/10.2174/0929867327666200312112412] [PMID: 32164504]
[87]
Zhang, H.; Zhao, H.Y.; Xi, X.X.; Liu, Y.J.; Xin, M.; Mao, S.; Zhang, J.J.; Lu, A.X.; Zhang, S.Q. Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC). Eur. J. Med. Chem., 2020, 189112061
[http://dx.doi.org/10.1016/j.ejmech.2020.112061] [PMID: 31951960]
[88]
Kargbo, R.B. Selective estrogen receptor degraders for the potential treatment of cancer. ACS Med. Chem. Lett., 2020, 11(4), 412-413.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00107] [PMID: 32292542]
[89]
Yang, C.Y.; Qin, C.; Bai, L.; Wang, S. Small-molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins - A review. Drug Discov. Today. Technol., 2019, 31, 43-51.
[http://dx.doi.org/10.1016/j.ddtec.2019.04.001] [PMID: 31200858]
[90]
Kargbo, R.B. PROTAC-mediated degradation of estrogen receptor in the treatment of cancer. ACS Med. Chem. Lett., 2019, 10(10), 1367-1369.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00397] [PMID: 31620216]
[91]
Shanmugasundaram, K.; Shao, P.; Chen, H.; Campos, B.; McHardy, S.F.; Luo, T.; Rao, H. A modular PROTAC design for target destruction using a degradation signal based on a single amino acid. J. Biol. Chem., 2019, 294(41), 15172-15175.
[http://dx.doi.org/10.1074/jbc.AC119.010790] [PMID: 31511327]
[92]
Bargagna-Mohan, P.; Baek, S.H.; Lee, H.; Kim, K.; Mohan, R. Use of PROTACS as molecular probes of angiogenesis. Bioorg. Med. Chem. Lett., 2005, 15(11), 2724-2727.
[http://dx.doi.org/10.1016/j.bmcl.2005.04.008]
[93]
Bennett, C. New oral compound can target & degrade the estrogen receptor. Oncol. Times, 2017, 39(3), 14-15.
[94]
Rodriguez-Gonzalez, A.; Cyrus, K.; Salcius, M.; Kim, K.; Crews, C.M.; Deshaies, R.J.; Sakamoto, K.M. Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene, 2008, 27(57), 7201-7211.
[http://dx.doi.org/10.1038/onc.2008.320] [PMID: 18794799]
[95]
Gonzalez, T.L.; Hancock, M.; Sun, S.; Gersch, C.L.; Larios, J.M.; David, W.; Hu, J.; Hayes, D.F.; Wang, S.; Rae, J.M. Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer. Breast Cancer Res. Treat., 2020, 180, 1-2.
[96]
Okuhira, K.; Demizu, Y.; Hattori, T.; Ohoka, N.; Shibata, N.; Nishimaki-Mogami, T.; Okuda, H.; Kurihara, M.; Naito, M. Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells. Cancer Sci., 2013, 104(11), 1492-1498.
[http://dx.doi.org/10.1111/cas.12272] [PMID: 23992566]
[97]
Okuhira, K.; Demizu, Y.; Hattori, T.; Ohoka, N.; Shibata, N.; Kurihara, M.; Naito, M. Molecular design, synthesis, and evaluation of SNIPER (ER) that induces proteasomal degradation of ERα.Estrogen Receptors; Humana Press: New York, NY, 2016, pp. 549-560.
[http://dx.doi.org/10.1007/978-1-4939-3127-9_42]
[98]
Ohoka, N.; Morita, Y.; Nagai, K.; Shimokawa, K.; Ujikawa, O.; Fujimori, I.; Ito, M.; Hayase, Y.; Okuhira, K.; Shibata, N.; Hattori, T.; Sameshima, T.; Sano, O.; Koyama, R.; Imaeda, Y.; Nara, H.; Cho, N.; Naito, M. Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation. J. Biol. Chem., 2018, 293(18), 6776-6790.
[http://dx.doi.org/10.1074/jbc.RA117.001091] [PMID: 29545311]
[99]
Zhang, F.; Wu, Z.; Chen, P.; Zhang, J.; Wang, T.; Zhou, J.; Zhang, H. Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide. Bioorg. Med. Chem., 2020, 28(1)115228
[http://dx.doi.org/10.1016/j.bmc.2019.115228] [PMID: 31813613]
[100]
Shi, Y.; Liu, J.; Zhao, Y.; Cao, J.; Li, Y.; Guo, F. Bromodomain-containing protein 4: a druggable target. Curr. Drug Targets, 2019, 20(15), 1517-1536.
[http://dx.doi.org/10.2174/1574885514666190618113519] [PMID: 31215391]