Division of Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Curr Opin Oncol. 2020 Sep;32(5):494-502. doi: 10.1097/CCO.0000000000000656.
Antibody-drug conjugates (ADCs) represent an interesting new class of anticancer agents, capable of exploiting the specificity of monoclonal antibodies toward cellular-antigens for a targeted release of potent cytotoxic drugs, with a potential increased activity and reduced toxicity compared with traditional chemotherapies. The aim of this article is to review the efficacy and safety of ADCs in breast cancer.
Following the approval of T-DM1 both in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel anti-HER2 ADCs have been investigated. Some of these compounds, such as the recently FDA-approved trastuzumab deruxtecan, have shown relevant activity in T-DM1-pretreated patients, possibly thanks to the so-called bystander effect, namely the ability to exert cytotoxic activity also against antigen-negative cells. Such feature allows to overcome the HER2 intratumoral heterogeneity in breast cancer and could explain in the preliminary activity demonstrated also in HER2-low breast cancers. However, several ADCs targeting other cancer-associated antigens than HER2 are under development, representing a promising strategy for the treatment of triple-negative tumors, exemplified by the encouraging results of sacituzumab govitecan.
ADCs are innovative and effective therapeutic drugs in breast cancer. Research efforts are ongoing to identify novel targets and combination with other treatment modalities, particularly with immunotherapy, to further improve patients' outcomes.
抗体药物偶联物（ADC）是一类很有前途的新型抗癌药物，能够利用单克隆抗体对细胞抗原的特异性，将有效且毒性低的细胞毒素药物靶向释放，与传统化疗相比，具有潜在的更高活性和更低毒性。本文旨在综述 ADC 在乳腺癌中的疗效和安全性。
在 T-DM1 被批准用于早期和晚期人类表皮生长因子受体 2（HER2）阳性乳腺癌后，新型抗 HER2 ADC 已被研究。其中一些化合物，如最近获得美国食品和药物管理局（FDA）批准的曲妥珠单抗德鲁替康，在 T-DM1 预处理患者中显示出相关活性，可能得益于所谓的旁观者效应，即对抗原阴性细胞也能发挥细胞毒性作用的能力。这种特性使得能够克服乳腺癌中 HER2 的肿瘤内异质性，也可以解释其在 HER2 低表达乳腺癌中初步显示出的活性。然而，有许多针对除 HER2 以外的其他癌相关抗原的 ADC 正在开发中，这代表了治疗三阴性肿瘤的一种很有前途的策略，例如 sacituzumab govitecan 的令人鼓舞的结果。
ADC 是乳腺癌中具有创新性和疗效的治疗药物。研究工作正在进行中，以确定新的靶点，并与其他治疗方式（特别是免疫疗法）联合应用，以进一步改善患者的预后。
