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Updated: Jan 11, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Genetic landscape and therapeutic evolution of cyclophosphamide: spotlight on breast cancer
Jiaoyan Cao1,2,3, Xin Xu4, Tao Lu5
1Department of Pathology, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
Cyclophosphamide is a chemotherapeutic agent widely used in breast cancer management. As a prodrug, its therapeutic efficacy and toxicity are profoundly influenced by host genetic variations that govern its metabolism, detoxification, DNA repair, and cellular transport mechanisms. This review examines pharmacogenomic landscape of cyclophosphamide in breast cancer, with focus on key genes and polymorphisms. A comprehensive literature review was conducted to identify genetic variants affecting cyclophosphamide metabolism (CYP2B6, CYP3A4, CYP3A5, CYP2C9, and CYP2C19), detoxification (ALDH1A1, GSTM1, GSTT1, and GSTP1), DNA repair (XRCC1, ERCC1, ERCC2, and MGMT), and transport (ABCB1 and SLCO1B1). Clinical correlations with drug response and adverse effects were analyzed. Polymorphisms in CYP2B6 (6, 9) and CYP3A5 (3) significantly alter activation and systemic exposure. Null variants in GSTM1 and GSTT1 are linked to increased drug toxicity due to impaired detoxification. DNA repair gene variants, such as XRCC1 Arg399Gln and ERCC2 Lys751Gln, influence treatment response and risk of side effects.
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