OncoTargets and Therapy (May 2022)

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

  • Liu X,
  • Zhou T,
  • Wang Y,
  • Pei M,
  • Wang G,
  • Chu W,
  • Wang Q,
  • Du S,
  • Wang H,
  • Wang C

Journal volume & issue
Vol. Volume 15
pp. 509 – 520

Abstract

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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 Du,3 Hongxia Wang,3 Chunhe Wang1,2,4 1Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3State 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; 4Research and Development Center, Dartsbio Pharmaceuticals, Zhongshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhe Wang, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Lane 720 Cai Lun Road, Bldg 1, Room 342, Shanghai, People’s Republic of China, Email [email protected] Hongxia Wang, Shanghai General Hospital, 650 Xinsongjiang Road, Shanghai, People’s Republic of China, Email [email protected]: 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, breast cancer, triple-negative breast cancer, antibody–drug conjugate, biomarker

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