Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: mechanisms, clinical applications, and future directions

Front Immunol. 2024 Nov 1:15:1495675. doi: 10.3389/fimmu.2024.1495675. eCollection 2024.

Abstract

Breast cancer remains a leading cause of cancer-related deaths among women worldwide, highlighting the need for novel therapeutic strategies. Trophoblast cell surface antigen 2 (Trop-2), a type I transmembrane glycoprotein highly expressed in various solid tumors including all subtypes of breast cancer, has emerged as a promising target for cancer therapy. This review focuses on recent advancements in Trop-2-targeted antibody-drug conjugates (ADCs) for breast cancer treatment. We comprehensively analyzed the structure and mechanism of action of ADCs, as well as the role of Trop-2 in breast cancer progression and prognosis. Several Trop-2-targeted ADCs, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-DXd), have demonstrated significant antitumor activity in clinical trials for both triple-negative breast cancer (TNBC) and hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. We systematically reviewed the ongoing clinical studies of these ADCs, highlighting their efficacy and safety profiles. Furthermore, we explored the potential of combining Trop-2-targeted ADCs with other therapeutic modalities, including immunotherapy, targeted therapies, and small molecule inhibitors. Notably, Trop-2-targeted ADCs have shown promise in reprogramming the tumor microenvironment through multiple signaling pathways, potentially enhancing antitumor immunity. This review aims to provide new insights and research directions for the development of innovative breast cancer therapies, offering potential solutions to improve treatment outcomes and quality of life for breast cancer patients.

Keywords: Datopotamab Deruxtecan; Sacituzumab Govitecan; Trop-2; antibody-drug conjugates; breast cancer; combination therapy; targeted therapy; tumor microenvironment 1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm* / immunology
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Camptothecin / analogs & derivatives
  • Cell Adhesion Molecules* / antagonists & inhibitors
  • Cell Adhesion Molecules* / immunology
  • Cell Adhesion Molecules* / metabolism
  • Female
  • Humans
  • Immunoconjugates* / pharmacology
  • Immunoconjugates* / therapeutic use
  • Molecular Targeted Therapy

Substances

  • TACSTD2 protein, human
  • Immunoconjugates
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • sacituzumab govitecan
  • Antineoplastic Agents, Immunological
  • Camptothecin
  • Antibodies, Monoclonal, Humanized

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the following funding sources: project of Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China (2023YJ014), General Program of Natural Science Foundation of Sichuan Province (2022NSFSC0814), the Talent Introduction Project of Mianyang Central Hospital (Grant number 2024RCYJ-001) and Mianyang Key Laboratory of Anesthesia and Neuroregulation (Grant number MZSJ202305).