scholarly journals Novel Therapies for Metastatic Triple-Negative Breast Cancer: Spotlight on Immunotherapy and Antibody-Drug Conjugates

ONCOLOGY ◽  
2021 ◽  
pp. 249-254
Author(s):  
Aiko Nagayama ◽  
Neelima Vidula ◽  
Aditya Bardia
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Novel Therapies ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Jason J. Zoeller ◽  
Aleksandr Vagodny ◽  
Veerle W. Daniels ◽  
Krishan Taneja ◽  
Benjamin Y. Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Negative Patient ◽  
Apoptotic Signaling ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Pdx Models ◽  
Antibody Drug

Abstract Background Targeted therapies for triple-negative breast cancer (TNBC) are limited; however, the epidermal growth factor receptor (EGFR) represents a potential target, as the majority of TNBC express EGFR. The purpose of these studies was to evaluate the effectiveness of two EGFR-targeted antibody-drug conjugates (ADC: ABT-414; ABBV-321) in combination with navitoclax, an antagonist of the anti-apoptotic BCL-2 and BCL-XL proteins, in order to assess the translational relevance of these combinations for TNBC. Methods The pre-clinical efficacy of combined treatments was evaluated in multiple patient-derived xenograft (PDX) models of TNBC. Microscopy-based dynamic BH3 profiling (DBP) was used to assess mitochondrial apoptotic signaling induced by navitoclax and/or ADC treatments, and the expression of EGFR and BCL-2/XL was analyzed in 46 triple-negative patient tumors. Results Treatment with navitoclax plus ABT-414 caused a significant reduction in tumor growth in five of seven PDXs and significant tumor regression in the highest EGFR-expressing PDX. Navitoclax plus ABBV-321, an EGFR-targeted ADC that displays more effective wild-type EGFR-targeting, elicited more significant tumor growth inhibition and regressions in the two highest EGFR-expressing models evaluated. The level of mitochondrial apoptotic signaling induced by single or combined drug treatments, as measured by DBP, correlated with the treatment responses observed in vivo. Lastly, the majority of triple-negative patient tumors were found to express EGFR and co-express BCL-XL and/or BCL-2. Conclusions The dramatic tumor regressions achieved using combined agents in pre-clinical TNBC models underscore the abilities of BCL-2/XL antagonists to enhance the effectiveness of EGFR-targeted ADCs and highlight the clinical potential for usage of such targeted ADCs to alleviate toxicities associated with combinations of BCL-2/XL inhibitors and systemic chemotherapies.

Antibody–drug conjugates in triple negative breast cancer

2018 ◽  
Vol 14 (25) ◽  
pp. 2651-2661 ◽  
Author(s):  
Nancy Tray ◽  
Sylvia Adams ◽  
Francisco J Esteva
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Antibody Drug

scholarly journals Novel antibody–drug conjugates for triple negative breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592091598 ◽  
Author(s):  
Aiko Nagayama ◽  
Neelima Vidula ◽  
Leif Ellisen ◽  
Aditya Bardia
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Clinical Development ◽  
Antibody Drug Conjugate ◽  
Drug Conjugates ◽  
Anti Cancer ◽  
Late Stages ◽  
Antibody Drug

Triple negative breast cancer (TNBC) is a heterogenous subtype of breast cancer often associated with an aggressive phenotype and poor prognosis. Antibody–drug conjugate (ADC), comprising of a monoclonal antibody linked to a cytotoxic payload by a linker, is gaining increasing traction as an anti-cancer therapeutic. Emerging ADC drugs such as sacituzumab govitecan (IMMU-132) and trastuzumab deruxtecan (DS-8201a) are in late stages of clinical development for patients with metastatic breast cancer, including TNBC. In this article, we review and discuss the development and clinical application of ADCs in patients with advanced TNBC.

scholarly journals Current state of clinical development of TROP2-directed antibody–drug conjugates for triple-negative breast cancer

2021 ◽  
Author(s):  
Maximilian Marhold
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Short Review ◽  
Clinical Development ◽  
Breast Cancers ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Current State ◽  
Epithelial Cell Marker ◽  
Antibody Drug

SummaryAntibody–drug conjugates (ADCs) against numerous molecular targets are currently being developed for the treatment of breast cancer (BCa). While the first ADC directed against Her2, namely trastuzumab–emtansine, was approved several years ago, targeting of TROP‑2, an epithelial cell marker overexpressed in approximately 80% of triple-negative breast cancers (TNBC) has gained interest through positive clinical data reported for the compound sacituzumab–govitecan (SG) resulting from the phase 3 ASCENT trial. This short review summarizes the data that led to approval of SG and to take a closer look at the state of clinical development of other ADCs targeting TROP‑2 in TNBC.

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