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Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Perspective

Antibody-drug Conjugates for Breast Cancer Treatment

Author(s): M. Saeed Sheikh* and Ying Huang

Volume 18, Issue 2, 2023

Published on: 27 September, 2022

Page: [108 - 113] Pages: 6

DOI: 10.2174/1574892817666220729121205

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Abstract

The use of antibody-drug conjugates is expected to transform the management of human malignancy. Antibody-drug conjugates for cancer treatment are designed to deliver anticancer drugs to tumor cells. The main components of such conjugates are a monoclonal antibody that binds to a tumor antigen, an anticancer drug to inhibit tumor cell growth and a linker that serves to conjugate the antibody and drug. The antibody-drug conjugates developed and approved for breast cancer treatment are ado-trastuzumab emtansine, (fam)-trastuzumab deruxtecan-nxki and sacituzumab govitecan. The mechanisms of action, clinical uses and toxic effects of these antibody-drug conjugates are discussed.

Keywords: Breast cancer, ado-trastuzumab emtansine, trastuzumab deruxtecan, sacituzumab govitecan, HER2, TROP-2.

[1]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics. CA Cancer J Clin 2021; 71(1): 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[3]
Allred DC, Wu Y, Mao S, et al. Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clin Cancer Res 2008; 14(2): 370-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1127] [PMID: 18223211]
[4]
Sgroi DC. Preinvasive breast cancer. Annu Rev Pathol 2010; 5(1): 193-221.
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092306] [PMID: 19824828]
[5]
Bombonati A, Sgroi DC. The molecular pathology of breast cancer progression. J Pathol 2011; 223(2): 307-17.
[http://dx.doi.org/10.1002/path.2808] [PMID: 21125683]
[6]
Sheikh MS, Satti SA. The emerging CDK4/6 inhibitor for breast cancer treatment. Mol Cell Pharmacol 2021; 13(3): 9-12.
[PMID: 35251463]
[7]
Dai X, Li T, Bai Z, et al. Breast cancer intrinsic subtype classification, clinical use and future trends. Am J Cancer Res 2015; 5(10): 2929-43.
[PMID: 26693050]
[8]
Allison KH. Molecular pathology of breast cancer: What a pathologist needs to know. Am J Clin Pathol 2012; 138(6): 770-80.
[http://dx.doi.org/10.1309/AJCPIV9IQ1MRQMOO] [PMID: 23161709]
[9]
An J, Sheikh MS. Toxicology of trastuzumab: An insight into mechanisms of cardiotoxicity. Curr Cancer Drug Targets 2019; 19(5): 400-7.
[http://dx.doi.org/10.2174/1568009618666171129222159] [PMID: 29189161]
[10]
Arienti C, Pignatta S, Tesei A. Epidermal growth factor receptor family and its role in gastric cancer. Front Oncol 2019; 9: 1308.
[http://dx.doi.org/10.3389/fonc.2019.01308] [PMID: 31850207]
[11]
Sheikh MS, Carrier F, Johnson AC, Ogdon SE, Fornace AJ Jr. Identification of an additional p53-responsive site in the human epidermal growth factor receptor gene promotor. Oncogene 1997; 15(9): 1095-101.
[http://dx.doi.org/10.1038/sj.onc.1201264] [PMID: 9285564]
[12]
Motamedi Z, Rajabi-Maham H, Azimzadeh Irani M. Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation-molecular dynamics study. J Mol Model 2021; 27(12): 361.
[http://dx.doi.org/10.1007/s00894-021-04986-9] [PMID: 34817689]
[13]
Tripathy D, Brufsky A, Cobleigh M, et al. De novo versus recurrent HER2-positive metastatic breast cancer: Patient characteristics, treatment, and survival from the SystHERs registry. Oncologist 2020; 25(2): e214-22.
[http://dx.doi.org/10.1634/theoncologist.2019-0446] [PMID: 32043771]
[14]
Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89(10): 4285-9.
[http://dx.doi.org/10.1073/pnas.89.10.4285] [PMID: 1350088]
[15]
Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res 2009; 15(24): 7479-91.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0636] [PMID: 20008848]
[16]
Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J. Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res 2001; 61(12): 4744-9.
[PMID: 11406546]
[17]
Petricevic B, Laengle J, Singer J, et al. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. J Transl Med 2013; 11(1): 307.
[http://dx.doi.org/10.1186/1479-5876-11-307] [PMID: 24330813]
[18]
Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004; 5(4): 317-28.
[http://dx.doi.org/10.1016/S1535-6108(04)00083-2] [PMID: 15093539]
[19]
Nami B, Maadi H, Wang Z. Mechanisms underlying the Action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer. Cancers (Basel) 2018; 10(10): 342.
[http://dx.doi.org/10.3390/cancers10100342] [PMID: 30241301]
[20]
De Mattos-Arruda L, Cortes J. Use of pertuzumab for the treatment of HER2-positive metastatic breast cancer. Adv Ther 2013; 30(7): 645-58.
[http://dx.doi.org/10.1007/s12325-013-0043-2] [PMID: 23881722]
[21]
Luo C, Chen S, Xu N, et al. Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties. Sci Rep 2017; 7(1): 46347.
[http://dx.doi.org/10.1038/srep46347] [PMID: 28397880]
[22]
Burstein HJ. Adjuvant systemic therapy for HER2-positive breast cancer 2021.https://www.uptodate.com/contents/adjuvant-systemic-therapy-for-her2-positive-breast-cancer
[23]
Anne F, Schott AF. Systemic treatment for HER2-positive metastatic breast cancer 2021.https://www.uptodate.com/contents/systemic-treatment-for-her2-positive-metastatic-breast-cancer
[25]
Highlights of prescribing information 2021.https://www.gene.com/download/pdf/perjeta_prescribing.pdf
[26]
Barok M, Joensuu H, Isola J. Trastuzumab emtansine: Mechanisms of action and drug resistance. Breast Cancer Res 2014; 16(2): 209.
[http://dx.doi.org/10.1186/bcr3621] [PMID: 24887180]
[27]
Kupchan SM, Komoda Y, Court WA, et al. Maytansine, a novel antileukemic ansa macrolide from Maytenus ovatus. J Am Chem Soc 1972; 94(4): 1354-6.
[http://dx.doi.org/10.1021/ja00759a054] [PMID: 5062169]
[28]
Kupchan SM, Komoda Y, Branfman AR, et al. The maytansinoids. Isolation, structural elucidation, and chemical interrelation of novel ansa macrolides. J Org Chem 1977; 42(14): 2349-57.
[http://dx.doi.org/10.1021/jo00434a001] [PMID: 874612]
[29]
Lopus M. Antibody-DM1 conjugates as cancer therapeutics. Cancer Lett 2011; 307(2): 113-8.
[http://dx.doi.org/10.1016/j.canlet.2011.03.017] [PMID: 21481526]
[30]
Highlights of prescribing information 2021. (Available from: https://www.gene.com/download/pdf/kadcyla_prescribing.pdf
[31]
Nakada T, Sugihara K, Jikoh T, Abe Y, Agatsuma T. The latest research and development into the antibody-drug conjugate, [fam-]trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo) 2019; 67(3): 173-85.
[http://dx.doi.org/10.1248/cpb.c18-00744] [PMID: 30827997]
[32]
Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA. Plant anti-tumor agents: The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca accuminata. J Am Chem Soc 1966; 88(16): 3888-90.
[http://dx.doi.org/10.1021/ja00968a057]
[34]
Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 2018; 9(48): 28989-9006.
[http://dx.doi.org/10.18632/oncotarget.25615] [PMID: 29989029]
[35]
Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 2015; 6(26): 22496-512.
[http://dx.doi.org/10.18632/oncotarget.4318] [PMID: 26101915]
[36]
Fornaro M, Dell’Arciprete R, Stella M, et al. Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas. Int J Cancer 1995; 62(5): 610-8.
[http://dx.doi.org/10.1002/ijc.2910620520] [PMID: 7665234]
[37]
Ripani E, Sacchetti A, Corda D, Alberti S. Human Trop-2 is a tumor-associated calcium signal transducer. Int J Cancer 1998; 76(5): 671-6.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19980529)76:5<671::AID-IJC10>3.0.CO;2-7] [PMID: 9610724]
[38]
Basu A, Goldenberg DM, Stein R. The epithelial/carcinoma antigen EGP-1, recognized by monoclonal antibody RS7-3G11, is phosphorylated on serine 303. Int J Cancer 1995; 62(4): 472-9.
[http://dx.doi.org/10.1002/ijc.2910620419] [PMID: 7635574]
[39]
Xu P, Zhao Y, Liu K, et al. Prognostic role and clinical significance of trophoblast cell surface antigen 2 in various carcinomas. Cancer Manag Res 2017; 9: 821-37.
[http://dx.doi.org/10.2147/CMAR.S147033] [PMID: 29276405]
[40]
Ambrogi F, Fornili M, Boracchi P, et al. Trop-2 is a determinant of breast cancer survival. PLoS One 2014; 9(5): e96993.
[http://dx.doi.org/10.1371/journal.pone.0096993] [PMID: 24824621]
[41]
Guerra E, Trerotola M, Dell’ Arciprete R, et al. A bicistronic CYCLIN D1-TROP2 mRNA chimera demonstrates a novel oncogenic mechanism in human cancer. Cancer Res 2008; 68(19): 8113-21.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6135] [PMID: 18829570]
[42]
Spring LM, Nakajima E, Hutchinson J, et al. Sacituzumab ovitecan for metastatic triple-negative breast cancer: Clinical overview and management of potential toxicities. Oncologist 2021; 26(10): 827-34.
[http://dx.doi.org/10.1002/onco.13878] [PMID: 34176192]
[43]

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