Apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 3B (APOBEC3B, A3B) is a key cytidine deaminase that induces genomic instability and clonal evolution in diverse malignancies. Although A3B plays a key role in the onset and advancement of various cancers, a comprehensive model bridging its multifaceted mechanisms and clinical translation is currently under‐characterized. This review synthesizes the molecular architecture, regulatory networks, and diverse oncogenic mechanisms of A3B. We demonstrate that A3B extends beyond its classical role as a DNA‐mutating enzyme by driving tumorigenesis through nonenzymatic pathways, such as the stabilization of c‐Myc. Furthermore, we evaluate the dual nature of A3B′s impact on the tumor immune microenvironment, where it simultaneously drives neoantigen‐mediated immune activation and promotes inhibitory immune evasion. Notably, this review positions A3B as an important biomarker for predicting therapeutic resistance while highlighting its potential in forecasting the efficacy of ATR inhibitors and immune checkpoint blockade (ICB). By identifying current research gaps and therapeutic opportunities, this review provides a systematic framework to guide the development of A3B‐targeted interventions and precision medicine strategies.
Zhou et al. (Thu,) studied this question.