Ddb2, also known as damage-specific DNA-binding protein 2, is initially identified as a DNA damage recognition factor crucial for global genomic nucleotide excision repair (GG-NER) in human cells. It is also involved in multiple essential biological processes such as chromatin remodeling, gene transcription, cell cycle regulation, and protein decay [1].

In cancer research, Ddb2 shows diverse roles. In pancreatic ductal adenocarcinoma (PDAC), its reduced expression in cancer tissues correlates with shorter disease-free survival. Overexpression of Ddb2 in PDAC cells represses epithelial-to-mesenchymal transition (EMT), reduces cell migration and invasion, and sensitizes cells to chemotherapy drugs like 5-fluorouracil, oxaliplatin, and gemcitabine, suggesting its tumor-suppressive effects [2]. In breast and ovarian teratoma tissues, high Ddb2 levels are associated with lower CDT2 levels, and Ddb2 regulates DNA replication by degrading CDT2 [3]. In lung adenocarcinoma (LUAD), MBD2 binds to the methylated CpG DNA within the DDB2 promoter to repress DDB2 expression, promoting tumor metastasis [4]. In hepatocellular carcinoma cells, TRABID deubiquitinates DDB2 to promote cell proliferation [5].

In conclusion, Ddb2 plays essential roles in DNA repair, cell cycle regulation, and protein degradation. Its study in cancer models reveals its potential as a prognostic biomarker and therapeutic target in various cancers, especially in PDAC, where it may help predict chemotherapy response and prognosis. Understanding Ddb2's functions contributes to a deeper comprehension of cancer development mechanisms and may guide the development of new cancer therapies.