Vassilis Gorgoulis and collaborators have recently published a paper in JECCR, where they elucidate a novel mechanism modulating resistance to androgen blockade therapy in prostate cancer. The authors identify a key GATA2-CDC6 signaling axis, where upon acquired resistance, the transcription factor GATA2 is endogenously downregulated, leading to direct stabilization of the CDC6 oncogene, activation of Epithelial-To-Mesenchymal transition (EMT) and abrogation of senescence. However, CDC6 inhibition is sufficient to reverse oncogenic features and establish senescence, offering a therapeutic window even after acquiring resistance to therapy.

Pubmed

A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer.
Mourkioti I, Polyzou A, Veroutis D, Theocharous G, Lagopati N, Gentile E, Stravokefalou V, Thanos DF, Havaki S, Kletsas D, Panaretakis T, Logothetis CJ, Stellas D, Petty R, Blandino G, Papaspyropoulos A, Gorgoulis VG.
J Exp Clin Cancer Res. 2023 Jul 29;42(1):187. doi: 10.1186/s13046-023-02769-z