DNA dC->dU-editing enzyme APOBEC-3A (A3A) (A3A)

DNA dC->dU-editing enzyme APOBEC-3A (A3A) is a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. Its primary biological role is in the innate immune system, where it restricts the replication of various viruses (such as HPV and HBV) and retrotransposons by deaminating cytosine to uracil in single-stranded DNA. However, its aberrant expression in many cancer types leads to widespread somatic mutations, characterized by specific mutational signatures (SBS2 and SBS13), which drive tumor evolution and the development of drug resistance. Consequently, A3A is an emerging therapeutic target in oncology, with strategies focusing on direct enzymatic inhibition or exploiting synthetic lethal vulnerabilities, such as those involving DNA polymerase theta (Polθ). While no clinical-stage inhibitors currently exist, research into small molecules like C8 and nucleic acid-based inhibitors like 2'-deoxyzebularine-containing oligonucleotides is active to mitigate its pro-mutagenic effects in cancer. Targeting A3A may prevent the acquisition of new mutations that allow tumors to escape therapy, thereby improving the durability of existing treatments. Additionally, A3A has been implicated in non-mutagenic pathways such as macrophage polarization, further expanding its role in the tumor microenvironment.

Other names

APOBEC3AApolipoprotein B mRNA editing enzyme catalytic subunit 3APhorbolin-1Single-stranded DNA cytosine deaminase

Cytidine deaminase inhibition