«Previous Article|Table of Contents|Next Article»

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2025 05

Page:

876-882

Research Field:

Publishing date:

Info

Title:

Application progress and prospect of antibody conjugated drugs in HER2 positive breast cancer

Author(s):

ZHAO Yan¹; 2; NIU Xiaoyu¹; 2; HAN Zengfeng¹; 2; CHA Chunyuan¹; 2; LI Wenjie¹; 2; SUN Binxu¹; 2

1.Department of Oncology,the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine£¬Tianjin 300381,China;2.National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China.

Keywords:

antibody conjugated drugs; HER2 positive; breast cancer

PACS:

R737.9

DOI:

10.3969/j.issn.1672-4992.2025.05.024

Abstract:

Breast cancer is one of the common malignant tumors in women.Human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients account for 20%~30% of the total number of breast cancer patients,and this subtype has the clinical characteristics of strong invasiveness,rapid progression,poor prognosis,low quality of survival and low survival rate,etc.Although the introduction of trastuzumab,a humanized monoclonal antibody targeting HER2,has changed its treatment landscape,it has also inevitably emerged.Antibody drug conjugate (ADC),as a new type of potential antitumor drug,utilizes monoclonal antibodies targeting tumor antigens to selectively deliver cytotoxic drugs to cancer cells,combining the selectivity of monoclonal antibodies with the cell-killing properties of payloads,which has the advantages of strong selectivity,high efficiency and low toxicity.At the same time,studies have shown that some ADCs have advantages in anti-HER2 targeted therapy resistance,therefore,in recent years,there has been significant progress in the targeted therapy of HER2-positive breast cancer,and this article focuses on the progress of the clinical application and the latest research of ADCs targeting HER2-positive breast cancer.

References:

£Û1£Ý BRAY F,LAVERSANNE M,SUNG H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries£ÛJ£Ý.CA Cancer J Clin,2024,74(3):229-263.
£Û2£Ý XIA C,DONG X,LI H,et al.Cancer statistics in China and United States,2022:profiles,trends,and determinants£ÛJ£Ý.Chin Med J,2022,135(5):584-590.
£Û3£Ý JOHNSON KS,CONANT EF,SOO MS.Molecular subtypes of breast cancer:A review for breast radiologists£ÛJ£Ý.J Breast Imaging,2021,3(1):12-24.
£Û4£Ý AL-THOUBAITY FK.Molecular classification of breast cancer:A retrospective cohort study£ÛJ£Ý.Ann Med Surg (Lond),2019£¬49:44-48.
£Û5£Ý OH DY,BANG YJ.HER2-targeted therapies-a role beyond breast cancer£ÛJ£Ý.Nat Rev Clin Oncol,2020,17(1):33-48.
£Û6£Ý CHUMSRI S,LI Z,SERIE DJ,et al.Incidence of late relapses in patients with HER2-positive breast cancer receiving adjuvant trastuzumab:Combined analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31£ÛJ£Ý.J Clin Oncol,2019,37(35):3425-3435.
£Û7£Ý LI BT,SHEN R,BUONOCORE D,et al.Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers:Results from a phase II basket trial£ÛJ£Ý.J Clin Oncol,2018£¬36(24):2532-2537.
£Û8£Ý TOLANEY SM,TAYOB N,DANG C,et al.Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT):A randomized clinical trial£ÛJ£Ý.J Clin Oncol,2021,39(21):2375-2385.
£Û9£Ý MANICH CS,O' SHAUGHNESSY J,AFTIMOS PG,et al.Primary outcome of the phase III SYD985.002/TULIP trial comparing £Ûvic-£Ýtrastuzumab duocarmazineto physician's choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer£ÛJ£Ý.Ann Oncol,2021,32£ºS1288.
£Û10£Ý MOLINA MA,CODONY-SERVAT J,ALBANELL J,et al.Trastuzumab (herceptin),a humanized anti-Her2 receptor monoclonal antibody,inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells£ÛJ£Ý.Cancer Res,2001,61(12):4744-4749.
£Û11£Ý NAGATA Y,LAN KH,ZHOU X,et al.PTEN activation contributes to tumor inhibition by trastuzumab,and loss of PTEN predicts trastuzumab resistance in patients£ÛJ£Ý.Cancer Cell,2004,6(2):117-127.
£Û12£Ý KLAPPER LN,WATERMAN H,SELA M,et al.Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2£ÛJ£Ý.Cancer Res,2000,60(13):3384-3388.
£Û13£Ý IZUMI Y,XU L,DI TOMASO E,et al.Tumour biology:herceptin acts as an anti-angiogenic cocktail£ÛJ£Ý.Nature,2002,416(6878):279-280.
£Û14£Ý CAPELAN M,PUGLIANO L,DE AZAMBUJA E,et al.Pertuzumab:new hope for patients with HER2-positive breast cancer£ÛJ£Ý.Ann Oncol,2013,24(2):273-282.
£Û15£Ý COLLINS DM,MADDEN SF,GAYNOR N,et al.Effects of HER family-targeting tyrosine kinase inhibitors on antibody-dependent cell-mediated cytotoxicity in HER2-expressing breast cancer£ÛJ£Ý.Clin Cancer Res,2021,27(3):807-818.
£Û16£Ý MEDINA PJ,GOODIN S.Lapatinib:a dual inhibitor of human epidermal growth factor receptor tyrosine kinases£ÛJ£Ý.Clin Ther,2008,30(8):1426-1447.
£Û17£Ý KONECNY GE,PEGRAM MD,VENKATESAN N,et al.Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells£ÛJ£Ý.Cancer Res,2006,66(3):1630-1639.
£Û18£Ý BURSTEIN HJ,SUN Y,DIRIX LY,et al.Neratinib,an irreversible ErbB receptor tyrosine kinase inhibitor,in patients with advanced ErbB2-positive breast cancer£ÛJ£Ý.J Clin Oncol,2010,28(8):1301-1307.
£Û19£Ý RITTER CA,PEREZ-TORRES M,RINEHART C,et al.Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network£ÛJ£Ý.Clin Cancer Res,2007£¬13(16):4909-4919.
£Û20£Ý EICHHORN PJ,GILI M,SCALTRITI M,et al.Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235£ÛJ£Ý.Cancer Res,2008,68(22):9221-9230.
£Û21£Ý CARRACEDO A,MA L,TERUYA-FELDSTEIN J,et al.Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer£ÛJ£Ý.J Clin Invest,2008,118(9):3065-3074.
£Û22£Ý HOFFMANN RM,COUMBE BGT,JOSEPHS DH,et al.Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs)£ÛJ£Ý.Oncoimmunology,2017,7(3):e1395127.
£Û23£Ý MARM¦I F.Antibody-drug conjugates for breast cancer£ÛJ£Ý.Oncol Res Treat,2022£¬45(1-2):26-36.
£Û24£Ý KHONGORZUL P,LING CJ,KHAN FU,et al.Antibody-drug conjugates:A comprehensive review£ÛJ£Ý.Mol Cancer Res£¬2020£¬18(1):3-19.
£Û25£Ý MARIANI G,FASOLO A,DE BENEDICTIS E,et al.Trastuzumab as adjuvant systemic therapy for HER2-positive breast cancer£ÛJ£Ý.Nat Clin Pract Oncol£¬2009£¬6(2):93-104.
£Û26£Ý MAITI R,PATEL B,PATEL N,et al.Antibody drug conjugates as targeted cancer therapy:past development,present challenges and future opportunities£ÛJ£Ý.Arch Pharm Res£¬2023£¬46(5):361-388.
£Û27£Ý ERICKSON HK,PARK PU,WIDDISON WC,et al.Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing£ÛJ£Ý.Cancer Res,2006,66(8):4426-4433.
£Û28£Ý XU Z,GUO D,JIANG Z,et al.Novel HER2-targeting antibody-drug conjugates of trastuzumab beyond T-DM1 in breast cancer:Trastuzumab deruxtecan(DS-8201a) and (Vic-)trastuzumab duocarmazine (SYD985)£ÛJ£Ý.Eur J Med Chem,2019,183:111682.
£Û29£Ý HUNTER FW,BARKER HR,LIPERT B,et al.Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer£ÛJ£Ý.Br J Cancer,2020£¬122(5):603-612.
£Û30£Ý LEWIS PHILLIPS GD,LI G,DUGGER DL,et al.Targeting HER2-positive breast cancer with trastuzumab-DM1,an antibody-cytotoxic drug conjugate£ÛJ£Ý.Cancer Res,2008,68(22):9280-9290.
£Û31£Ý KROP IE,KIM SB,GONZ¦BLEZ-MART¦PN A,et al.Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA):a randomised,open-label,phase 3 trial£ÛJ£Ý.Lancet Oncol,2014,15(7):689-699.
£Û32£Ý VON MINCKWITZ G,HUANG CS,MANO MS,et al.Trastuzumab emtansine for residual invasive HER2-positive breast cancer£ÛJ£Ý.N Engl J Med,2019,380(7):617-628.
£Û33£Ý VERMA S,MILES D,GIANNI L,et al.Trastuzumab emtansine for HER2-positive advanced breast cancer£ÛJ£Ý.N Engl J Med,2012,367(19):1783-1791.
£Û34£Ý CORT¦IS J,KIM SB,CHUNG WP,et al.Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer£ÛJ£Ý.N Engl J Med,2022,386(12):1143-1154.
£Û35£Ý TAMURA K,TSURUTANI J,TAKAHASHI S,et al.Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine:a dose-expansion,phase 1 study£ÛJ£Ý.Lancet Oncol,2019,20(6):816-826.
£Û36£Ý NARAYAN P,OSGOOD CL,SINGH H,et al.FDA approval summary:Fam-Trastuzumab Deruxtecan-Nxki for the treatment of unresectable or metastatic HER2-positive breast cancer£ÛJ£Ý.Clin Cancer Res,2021,27(16):4478-4485.
£Û37£Ý MODI S,JACOT W,YAMASHITA T,et al.Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer£ÛJ£Ý.N Engl J Med,2022,387(1):9-20.
£Û38£Ý BANERJI U,VAN HERPEN CML,SAURA C,et al.Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer:a phase 1 dose-escalation and dose-expansion study£ÛJ£Ý.Lancet Oncol,2019,20(8):1124-1135.
£Û39£Ý HUANG L,WANG R,XIE K,et al.A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation£ÛJ£Ý.Breast Cancer Res Treat£¬2022£¬191(1):51-61.
£Û40£Ý BAROK M,LE JONCOUR V,MARTINS A,et al.ARX788,a novel anti-HER2 antibody-drug conjugate,shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer£ÛJ£Ý.Cancer Lett£¬2020£¬473:156-163.
£Û41£Ý SKIDMORE LILLIAN.ARX788,a site-specific anti-HER2 antibody-drug conjugate,demonstrates potent and selective activity in HER2-low and T-DM1-resistant breast and gastric cancers£ÛJ£Ý.Molecular Cancer Therapeutics,2020,19(9):1833-1843.
£Û42£Ý LIU Y£¬LIAN W£¬ZHAO X£¬et al.A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies£ÛJ£Ý.J Clin Oncol£¬2020,38£º1049.
£Û43£Ý OGANESYAN V,PENG L,BEE JS,et al.Structural insights into the mechanism of action of a biparatopic anti-HER2 antibody£ÛJ£Ý.J Biol Chem,2018,293(22):8439-8448.
£Û44£Ý WANG J,LIU Y,ZHANG Q,et al.Rc48-adc,a her2-targeting antibody-drug conjugate,in patients with her2-positive and her2-low expressing advanced or metastatic breast cancer:A pooled analysis of two studies£ÛJ£Ý.Clin Oncol,2021,39(15_suppl):1022.
£Û45£Ý JOHNSON KS,CONANT EF,SOO MS.Molecular subtypes of breast cancer:a review for breast radiologists£ÛJ£Ý.J Breast Imaging,2021,3(1):12-24.
£Û46£Ý DRAGO JZ,MODI S,CHANDARLAPATY S.Unlocking the potential of antibody-drug conjugates for cancer therapy£ÛJ£Ý.Nat Rev Clin Oncol,2021,18(6):327-344.

Memo

Memo:

Ìì½òÖÐÒ½Ò©´óѧÑо¿Éú¿ÆÑд´ÐÂÏîÄ¿£¨±àºÅ:YJSKC-20232001£©

Common functions

Last Update: 1900-01-01