TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer

Xiaoyue Liu; Tianhao Zhou; Yongmei Wang; Min Pei; Guifeng Wang; Wendi Chu; Qi Wang; Shaoqian Du; Hongxia Wang; Chunhe Wang

doi:10.2147/OTT.S354048

TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer

Onco Targets Ther. 2022 May 3:15:509-520. doi: 10.2147/OTT.S354048. eCollection 2022.

Authors

Xiaoyue Liu^#^{1

2}, Tianhao Zhou^#³, Yongmei Wang^{1

2}, Min Pei^{1

2}, Guifeng Wang^{1

2}, Wendi Chu^{1

2}, Qi Wang^{1

2}, Shaoqian Du³, Hongxia Wang³, Chunhe Wang^{1

2

4}

Affiliations

¹ Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
² University of Chinese Academy of Sciences, Beijing, People's Republic of China.
³ State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
⁴ Research and Development Center, Dartsbio Pharmaceuticals, Zhongshan, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC.

Methods: The levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload.

Results: TROP2 overexpression was identified in significantly more (P = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more (P = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients.

Conclusion: Our results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival.

Keywords: TROP2; antibody–drug conjugate; biomarker; breast cancer; triple-negative breast cancer.

Grants and funding

This work was supported by the China National Major Scientific and Technological Special Project for “Significant New Drugs Innovation and Development” (2019ZX09732002-006), the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDA12020223, XDA12020330), the National Natural Science Foundation of China (81872785 and 81673347), Shanghai Municipal Commission of Science and Technology of China (17431904400, 19YF1457400 and 21S11904500), Institutes for Drug Discovery and Development, Chinese Academy of Sciences (CASIMM0120202007), and Major Scientific and Technological Special Project of Zhongshan City (191022172638719, 210205143867019).