Mechanisms of action and resistance to anti-HER2 antibody-drug conjugates in breast cancer

被引：12

作者：

Saleh, Khalil ^{[1
]}

Khoury, Rita ^{[1
]}

Khalife, Nadine ^{[2
]}

Chahine, Claude ^{[1
]}

Ibrahim, Rebecca ^{[1
]}

Tikriti, Zamzam ^{[1
]}

Le Cesne, Axel ^{[1
]}

机构：

[1] Gustave Roussy Canc Campus, Int Dept, 114 Rue Edouard Vaillant, F-94800 Villejuif, France

[2] Gustave Roussy Canc Campus, Dept Head & Neck Oncol, F-94800 Villejuif, France

来源：

CANCER DRUG RESISTANCE | 2024年 / 7卷

关键词：

Trastuzumab; pertuzumab; trastuzumab emtansine; antibody-drug conjugate (ADC); trastuzumab deruxtecan; metastatic breast cancer; HER2; resistance; TRASTUZUMAB EMTANSINE T-DM1; OPEN-LABEL; PHASE-III; ADC; PERTUZUMAB; EFFICACY; PLUS; DERUXTECAN; ATEZOLIZUMAB; MULTICENTER;

D O I：

10.20517/cdr.2024.06

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human epidermal growth factor 2 (HER2)-positive breast cancer (BC) represents nearly 20% of all breast tumors. Historically, these patients had a high rate of relapse and dismal prognosis. The advent of HER2targeting monoclonal antibodies such as trastuzumab followed by pertuzumab had improved the prognosis of HER2-positive metastatic BC. More recently, antibody-drug conjugates (ADCs) are now reshaping the treatment paradigm of solid tumors, especially breast cancer. Tratsuzumab emtansine (T-DM1) was one of the first ADC developed in oncology and was approved for the management of HER2-positive metastatic BC. In a head-to-head comparison, trastuzumab deruxtecan (T-DXd) defeated T-DM1 as a second-line treatment. The efficacy of ADCs is counterbalanced by the appearance of acquired resistance to these agents. In this paper, we summarize the mechanisms of action and resistance of T-DM1 and T-DXd, as well as their clinical efficacy. Additionally, we also discuss potential strategies for addressing resistance to ADC.

引用

页码：2 / 15

页数：15

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