55484 Dual activation of CAR and Nrf2 improves the efficacy: toxicity ratio of cyclophosphamide and doxorubicin-based treatment of TNBC

55484 Dual activation of CAR and Nrf2 improves the efficacy: toxicity ratio of cyclophosphamide and doxorubicin-based treatment of TNBC

ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxor...

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Bibliographic Details
Main Authors: Sydney Stern, Dongdong Liang, Linhao Li, Ritika Kurian, Caitlin Lynch, Scott Heyward, Ajoke Kareem, Young Chun, Charles Hong, Fengtian Xue, Hongbing Wang
Format: Article
Language:English
Published: Cambridge University Press 2021-03-01
Series:Journal of Clinical and Translational Science
Online Access:https://www.cambridge.org/core/product/identifier/S2059866121006531/type/journal_article
Description
Summary:ABSTRACT IMPACT: Triple negative breast cancer (TNBC) affects 10-20% of women with breast cancer and is biologically more aggressive than other subtypes. The novel compound we have developed, DL7076, would give clinicians a vital strategy to improve the commonly used cyclophosphamide (CPA) and doxorubicin (DOX) regimen in the treatment of TNBC. OBJECTIVES/GOALS: The objective of this research project is to develop a novel compound which can activate both 1) the constitutive androstane receptor (CAR) and subsequently enhance the CYP2B6-mediated activation of CPA, and 2) the nuclear factor erythroid- related factor-2 (Nrf2) leading to the cardiomyocyte protection from DOX-associated cardiotoxicity. METHODS/STUDY POPULATION: Following the identification of the compound candidate, DL7076 was evaluated for tissue specific induction of CAR and Nrf2 using qPCR, western blot analysis, and luciferase reporter assays.
ISSN:2059-8661

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