Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer

Abstract

Breast cancer continues to have a high incidence rate among female malignancies. Despite significant advancements in treatment modalities, the heterogeneous nature of breast cancer and its resistance to various therapeutic approaches pose considerable challenges. Antibody-drug conjugates (ADCs) effectively merge the specificity of antibodies with the cytotoxicity of chemotherapeutic agents, offering a novel strategy for precision treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) has provided a new therapeutic option for HER2-positive breast cancer patients globally, especially those resistant to conventional treatments. The development of trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) has further broadened the applicability of ADCs in breast cancer therapy, presenting new hopes for patients with low HER2 expression and triple-negative breast cancer. However, the application of ADCs presents certain challenges. For instance, their treatment may lead to adverse reactions such as interstitial lung disease, thrombocytopenia, and diarrhea. Moreover, prolonged treatment could result in ADCs resistance, complicating the therapeutic process. Economically, the high costs of ADCs might hinder their accessibility in low-income regions. This article reviews the structure, mechanism of action, and clinical trials of commercially available ADCs for breast cancer treatment, with a focus on the clinical trials of the three drugs, aiming to provide insights for clinical applications and future research.

Keywords: ADC; SG; T-DM1; T-DXd; breast cancer.

FIGURE 1

Structural and mechanistic sketch of T-DM1 and T-DXd. (A) Structure of T-DM1 and T-DXd. (B) Mechanism of action of T-DM1 and T-DXd.

FIGURE 2

Structural and mechanistic sketch of SG. (A) Structure of SG. (B) Mechanism of action of SG.