ETS-related gene (ERG) (ERG)

ETS-related gene (ERG) is a member of the ETS (erythroblast transformation-specific) family of transcription factors that serves as a key regulator of gene expression involved in cell proliferation, differentiation, and development [3, 12]. Under normal physiological conditions, ERG is essential for maintaining hematopoiesis, vascular integrity, and angiogenesis [5, 11, 13]. However, it is widely recognized as a potent oncogene, most notably in prostate cancer, where the TMPRSS2-ERG gene fusion occurs in approximately 50% of cases, leading to the aberrant, androgen-driven overexpression of the ERG protein [1, 6, 7]. This overexpression drives oncogenic processes such as the epithelial-mesenchymal transition (EMT), increased cell motility, and invasion, contributing to tumor progression and metastasis [6, 14, 16]. Beyond prostate cancer, ERG fusions are also implicated in Ewing sarcoma and certain types of leukemia, such as acute myeloid leukemia (AML) [3, 4, 8]. Although transcription factors like ERG have historically been challenging to target with small molecules, emerging therapeutic strategies include the development of DNA-binding inhibitors, peptidomimetic degraders, and inhibitors of its co-regulatory partners [2, 4, 14, 15]. Targeting ERG remains a high-priority goal in precision oncology, particularly for patients harboring the TMPRSS2-ERG rearrangement [2, 7].

Other names

p55 [3, 12]ERG-1 [3]ERG-2 [3]ERG-3 [3, 12]v-ets avian erythroblastosis virus E26 oncogene homolog [3, 12]ETS transcription factor ERG [12]Transcriptional regulator ERG [12]Transforming protein ERG [12]

Inhibition of ERG-DNA binding, induction of proteasomal degradation of ERG protein, and disruption of protein-protein interactions with co-regulators such as DNA-PK, PARP1, and KDM4A [2, 4, 14, 15].