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Original Publication Date
2026
Document Type
Video
Abstract
Breast cancer is one of the most common cancers worldwide, with approximately one in eight women expected to be diagnosed during their lifetime. Among breast cancer subtypes, Triple-Negative Breast Cancer (TNBC) is particularly aggressive and difficult to treat because it lacks the hormone and receptor markers that enable targeted therapies in other subtypes. As a result, identifying effective treatments and understanding mechanisms of drug resistance remain critical challenges.
This research investigates resistance to Sacituzumab-Govitecan, an antibody–drug conjugate designed to selectively deliver a cytotoxic payload to cancer cells expressing the Trop-2 protein. Using patient-derived tumor samples implanted into immunocompromised mouse models, the study evaluated the therapeutic response of multiple TNBC models to this treatment. Tumor inhibition analysis revealed both drug-sensitive and drug-resistant tumors, indicating variability in treatment effectiveness across patient-derived models.
To investigate mechanisms of resistance, additional acquired-resistance models were generated through repeated drug exposure. Functional assays were then used to distinguish between two primary resistance pathways: antibody-mediated resistance, in which cancer cells reduce internalization of the antibody–drug conjugate, and payload-mediated resistance, in which tumor cells develop resistance to the cytotoxic drug component. Experimental results demonstrated that resistant models exhibited either reduced drug internalization or decreased sensitivity to the payload, highlighting distinct biological mechanisms underlying treatment failure.
These findings emphasize the heterogeneity of TNBC and the importance of identifying predictive biomarkers for treatment response. Ongoing work aims to define gene expression signatures that distinguish sensitive from resistant tumors, enabling clinicians to select the most effective therapy for individual patients at the outset of treatment. Such predictive strategies may improve therapeutic outcomes and help overcome drug resistance in aggressive breast cancers.
Keywords
Triple-Negative Breast Cancer, Sacituzumab Govitecan, Antibody–drug conjugates, Drug resistance
Rights
Copyright © 2026 Carson Walker. All rights reserved.
Comments
Presented in the Advancements in Targeted Cancer Therapeutics session.