Division of Oncology, Children's Hospital of Philadelphia, United States; Division of Infectious Diseases, Children's Hospital of Philadelphia, United States; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, United States; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, United States; Department of Pediatrics, Washington University School of Medicine, United States.
Center for Childhood Cancer Research, Children's Hospital of Philadelphia, United States; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, United States.
DNA Repair (Amst). 2019 Nov;83:102700. doi: 10.1016/j.dnarep.2019.102700. Epub 2019 Sep 13.
The APOBEC3 family of cytosine deaminases are part of the innate immune response to viral infection, but also have the capacity to damage cellular DNA. Detection of mutational signatures consistent with APOBEC3 activity, together with elevated APOBEC3 expression in cancer cells, has raised the possibility that these enzymes contribute to oncogenesis. Genome deamination by APOBEC3 enzymes also elicits DNA damage response signaling and presents therapeutic vulnerabilities for cancer cells. Here, we discuss implications of APOBEC3 activity in cancer and the potential to exploit their mutagenic activity for targeted cancer therapies.
APOBEC3 家族的胞嘧啶脱氨酶是先天免疫反应病毒感染的一部分，但也有能力损害细胞 DNA。在癌细胞中检测到与 APOBEC3 活性一致的突变特征，并同时检测到 APOBEC3 表达升高，这增加了这些酶促进致癌的可能性。APOBEC3 酶对基因组的脱氨作用也会引发 DNA 损伤反应信号，并为癌细胞提供治疗上的弱点。在这里，我们讨论了 APOBEC3 活性在癌症中的意义，以及利用其诱变活性进行靶向癌症治疗的潜力。
