Trop2-Based Antibody-Drug Conjugates: Emerging Strategy and Progress in Triple-Negative Breast Cancer Therapy

Sep 22, 2026

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Triple-negative breast cancer (TNBC) represents a highly heterogeneous and aggressive subtype accounting for 15–20% of invasive cases, with limited options and poor prognosis. Trophoblast cell-surface antigen 2 (Trop2) is calcium-signal related and frequently overexpressed in TNBC (~88%) while showing minimal normal-tissue expression, and high Trop2 levels correlate with invasion, metastasis, and unfavorable outcomes. Trop2-targeted antibody–drug conjugates (ADCs) show strong clinical potential. This review systematically summarizes clinical research progress to support evidence-based prognostic improvement for TNBC patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Trop2 as a Target for TNBC

ADCs and Clinical Progress

Next-Generation Trop2-Targeted Agents

Review Trop2-Based Antibody–Drug Conjugates: Emerging Strategy and Progress in Triple-Negative Breast Cancer Therapy Tong Li 1, Tao Zhang 2, Yongxia Dang 1, Yilin Lin 1, Xiaotong Li 1 and Xiaoling Ling 2, * Received: 12 November 2025 Revised: 16 January 2026 Accepted: 26 January 2026 Published: 3 February 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 The First Clinical Medical College, Lanzhou University, No. 199 Donggang West Road, Lanzhou 730000, China; [lit2024@lzu.edu.cn](lit2024@lzu.edu.cn) (T.L.); [dangyx2023@lzu.edu.cn](dangyx2023@lzu.edu.cn) (Y.D.); [linyl2024@lzu.edu.cn](linyl2024@lzu.edu.cn) (Y.L.); [lxiaotong2024@lzu.edu.cn](lxiaotong2024@lzu.edu.cn) (X.L.) 2 Department of Oncology, The First Hospital of Lanzhou University, No. 1 Donggang West Road, Lanzhou 730000, China; [zhangt18@lzu.edu.cn](zhangt18@lzu.edu.cn) * Correspondence: [ldyy_lingxl@lzu.edu.cn](ldyy_lingxl@lzu.edu.cn) Simple Summary With the aim of providing evidence-based insights for improved prognosis in TNBC patients, this article conducts a systematic review of the clinical research progress of Trop2-targeted ADCs. Trop2-targeted therapies are set to become a cornerstone of precision medicine for solid tumors, thereby paving the way for superior treatment options for patients. Abstract Triple-negative breast cancer (TNBC) accounts for 15–20% of invasive breast cancers and represents a highly heterogeneous, aggressive subtype with poor prognosis and limited treatment options, necessitating the identification of novel therapeutic targets to improve clinical outcomes. Trophoblast cell-surface antigen 2 (Trop2), a calcium signal transducer, is frequently overexpressed in TNBC (approximately 88% of cases) while exhibiting minimal expression in normal tissues. Its overexpression is significantly associated with tumor invasion, metastasis, and unfavorable prognosis. Antibody–drug conjugates (ADCs) targeting Trop2 have demonstrated significant clinical potential. This article systematically reviews the clinical research progress of Trop2-targeted ADCs, aiming to provide evidence-based insights for improving the prognosis of TNBC patients. Keywords: triple-negative breast cancer (TNBC); Trophoblast cell-surface antigen 2 (Trop2); antibody–drug conjugates (ADCs); targeted therapy; clinical research 1. Introduction As the most common malignant tumor in women, breast cancer constitutes 32% of new cancer cases according to the 2025 Global Cancer Statistics Report, representing the leading component of female cancer incidence [1] . Among breast cancer subtypes, triple-negative breast cancer (TNBC) is characterized by the lack of established therapeutic targets and insensitivity to endocrine and targeted therapies. This results in limited treatment options and a typically poor prognosis [2–4] . It is important to consider immunotherapy and Poly (ADP-ribose) Polymerase inhibitors (PARPi) as standard treatment options, which have been shown to improve the prognosis of TNBC. However, a substantial unmet clinical need remains for the broader TNBC population, particularly for patients with treatment-resistant or recurrent/metastatic disease [5] . This pressing situation underscores the urgent necessity to explore novel therapeutic targets and mechanisms of action. Antibody–drug conjugates (ADCs), which combine a targeted antibody with a potent cytotoxic payload, offer a paradigm shift in cancer therapy by enabling precise delivery of chemotherapy to tumor cells [6] . Against this backdrop, Trophoblast cell-surface antigen 2 (Trop2), a type I transmembrane glycoprotein belonging to the tumor-associated calcium signal transducer (TACSTD) family, has emerged as an ideal target for ADC development [7,8] . Its suitability as a target rests on several key features: First, Trop2

FAQs

Why is TNBC considered difficult to treat, and what clinical needs remain?

TNBC lacks established therapeutic targets and shows insensitivity to endocrine and targeted therapies, leading to limited options and poor prognosis. There is an unmet need for novel targets, especially for patients with treatment-resistant or recurrent/metastatic disease.

What makes Trop2 a suitable target for antibody–drug conjugates in TNBC?

Trop2 is extremely low in normal tissues but highly and stably expressed on membranes of epithelial-derived malignancies, including TNBC (~88%). Its overexpression is linked to aggressive behavior, metastasis, and poor prognosis, and supports ADC efficacy through internalization and payload delivery.

What role do Trop2-targeted ADC design differences play in efficacy and safety?

Differences such as linker chemistry, payload class, and drug-to-antibody ratio (DAR) translate into distinct efficacy and safety profiles. They also contribute to different potential resistance mechanisms, making comparative clinical synthesis important.

Sep 22, 2026

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