Background: Trophoblast cell-surface antigen 2 (TROP2) is related to tumor proliferation enhancement and poor prognosis. An antibody targeting TROP2 was developed to treat metastatic triple-negative breast cancer (TNBC) which has a limited treatment modality. To characterize the TROP2 expressing tumors in TNBC, we analyzed TROP2 expression in three cohorts; (1) primary tumor without neoadjuvant chemotherapy, (2) primary tumor with neoadjuvant chemotherapy, and (3) metastatic tumor.
Methods: A total of 807 TNBC cases were evaluated for TROP2 immunohistochemical expression. We evaluated the TROP2 H-score distribution in the three cohorts. Tumors were divided into two groups based on TROP2 expression (high vs. low). We analyzed the relationship between clinicopathologic features and markers, including epidermal growth factor receptor, cytokeratin 5/6, p53, and Ki-67, and prognostic significance at high vs. low TROP2 expression.
Results: There was no difference in TROP2 H-score distribution between the three cohorts. Moderate-to-strong membranous expression of TROP2 in at least 10% of tumor cells was present in 662 cases (82.0%) in Cohort 1, 59 cases (89.4%) in Cohort 2, and 23 cases (88.5%) in Cohort 3. There was no significant difference in clinicopathologic features between high vs. low TROP2 in all cohorts. TROP2 H-score was an independent poor prognostic factor for overall survival in Cohort 3.
Conclusions: TNBC showed similar TROP2 expression regardless of neoadjuvant treatment or primary tumor/metastasis. Although the prognostic significance of TROP2 expression in metastatic TNBC has been revealed, further evaluation of the predictive value of TROP2 expression for targeted therapy is needed.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509625 | PMC |
http://dx.doi.org/10.1186/s12885-022-10076-7 | DOI Listing |
Int J Mol Sci
December 2024
Department of Oncology, University Hospital of Udine, 33100 Udine, Italy.
Antibody-drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (), human epidermal growth factor receptor 3 (), trophoblast cell surface antigen 2 (), Mesenchymal-epithelial transition factor (), and carcinoembryonic antigen-related cell adhesion molecule 5 (). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs.
View Article and Find Full Text PDFMol Cancer Ther
December 2024
OBI Pharma, Inc., Taipei, Taiwan.
Trophoblast cell surface antigen 2 (TROP2) is highly expressed in multiple cancers relative to normal tissues, supporting its role as a target for cancer therapy. OBI-992 is an antibody-drug conjugate (ADC) derived from a novel TROP2-targeted antibody linked to the topoisomerase 1 (TOP1) inhibitor exatecan via an enzyme-cleavable hydrophilic linker, with a drug-antibody ratio of 4. This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD.
View Article and Find Full Text PDFFront Immunol
December 2024
Myeloid Therapeutics, Inc., Cambridge, MA, United States.
Introduction: The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of B cell malignancies has fueled the development of numerous cell therapies. However, these cell therapies are complex and costly, and unlike in hematological malignancies, outcomes with most T cell therapies in solid tumors have been disappointing. Here, we present a novel approach to directly program myeloid cells by administering novel TROP2 CAR mRNA encapsulated in lipid nanoparticles (LNPs).
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Pinotbio, Inc Suwon, Gyeonggi-do 16506, South Korea.
FL118, a camptothecin derivative with dual mechanisms of action through topoisomerase I inhibition and proteasome-mediated degradation of anti-apoptotic proteins exhibits potent anti-tumor activity while remaining resistant to drug efflux transporters. This work describes the targeted delivery of FL118 to tumors via antibody-drug conjugates (ADCs) using the pH-sensitive CL2A linker. ADCs targeting Trop2, HER2, and EGFR exhibited potent in vitro cytotoxicity, with IC values as low as 0.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!