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Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer
Pieter A Roelofs1,2, John W M Martens3, Reuben S Harris2,4,5
1Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Abstract:
Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intratumor and intertumor genomic heterogeneity and therapy resistance in, among others, breast cancer. Understanding the available methods for clinical detection of these enzymes, the conditions required for their (dysregulated) expression, the clinical impact they have, and the clinical implications they may offer is crucial in understanding the current impact of APOBEC3-mediated mutagenesis in breast cancer. Here, we provide a comprehensive review of recent developments in the detection of APOBEC3-mediated mutagenesis and responsible APOBEC3 enzymes, summarize the pathways that control their expression, and explore the clinical ramifications and opportunities they pose. We propose that APOBEC3-mediated mutagenesis can function as a helpful predictive biomarker in several standard-of-care breast cancer treatment plans and may be a novel target for treatment.
Insights
APOBEC3 enzymes drive cancer mutations and resistance, particularly in breast cancer. Detecting APOBEC3 activity could offer new biomarkers and therapeutic targets for improved cancer treatment.
Area of Science:
- Biochemistry and Molecular Biology
- Genetics and Genomics
- Oncology
Background:
- The APOBEC3 (apolipoprotein B mRNA editing catalytic polypeptide-like 3) family of cytosine deaminases is increasingly recognized for its role in cancer genome mutagenesis.
- This mutagenesis contributes to genomic heterogeneity within and between tumors, impacting therapeutic resistance in various cancers, including breast cancer.
Approach:
- This review comprehensively examines recent advancements in detecting APOBEC3-mediated mutagenesis.
- It summarizes the regulatory pathways controlling APOBEC3 enzyme expression.
- The clinical impact and potential therapeutic opportunities presented by APOBEC3 enzymes are explored.
Key Points:
- APOBEC3 enzymes are significant drivers of cancer genome mutations.
- Dysregulated APOBEC3 expression is linked to intratumor heterogeneity and therapy resistance.
- Understanding APOBEC3 detection methods and expression is crucial for clinical applications.
Conclusions:
- APOBEC3-mediated mutagenesis shows promise as a predictive biomarker in breast cancer treatment.
- APOBEC3 enzymes represent a potential novel therapeutic target for cancer therapy.
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