Drug-resistant profiles of extracellular vesicles predict therapeutic response in TNBC patients receiving neoadjuvant chemotherapy

Abstract

Abstract Background Predicting tumor responses to neoadjuvant chemotherapy (NAC) is critical for evaluating prognosis and designing treatment strategies for patients with breast cancer; however, there are no reliable biomarkers that can effectively assess tumor responses. Therefore, we aimed to evaluate the clinical feasibility of using extracellular vesicles (EVs) to predict tumor response after NAC. Methods Drug-resistant triple-negative breast cancer (TNBC) cell lines were successfully established, which developed specific morphologies and rapidly growing features. To detect resistance to chemotherapeutic drugs, EVs were isolated from cultured cells and plasma samples collected post-NAC from 36 patients with breast cancer. Results Among the differentially expressed gene profiles between parental and drug-resistant cell lines, drug efflux transporters such as MDR1, MRP1, and BCRP were highly expressed in resistant cell lines. Drug efflux transporters have been identified not only in cell lines but also in EVs released from parental cells using immunoaffinity-based EV isolation. The expression of drug resistance markers in EVs was relatively high in patients with residual disease compared to those with a pathological complete response. Conclusions The optimal combination of drug-resistant EV markers was significantly efficient in predicting resistance to NAC with 81.82% sensitivity and 92.86% specificity.

Keywords

• TNBC
• Neoadjuvant chemotherapy
• Liquid biopsy
• Predictive biomarker
• Extracellular vesicles