UNG (Uracil DNA Glycosylase)

Furthermore, ΔUNG tumor cells had altered sensitivity to exogenous interferons in vitro, with increased sensitivity to IFN-γ but decreased sensitivity to IFN-α/β. Collectively, our data show that tumor-cell-specific UNG deficiency results in an altered tumor microenvironment in vivo and provide proof of concept for the use of UNG inhibitors to modulate inflammatory pathways in tumors.

Furthermore, ΔUNG tumor cells have altered sensitivity to exogenous interferons in vitro , with increased sensitivity to IFN-γ but decreased sensitivity to IFN-α/β. Collectively, our data show that tumor cell-specific UNG deficiency results in an altered tumor microenvironment in vivo and provide proof-of-concept data for the use of UNG inhibitors to modulate inflammatory pathways in tumors.

Uracil DNA glycosylase (UNG) excises uracil and 5-fluorouracil bases from DNA and is implicated in fluorodeoxyuridine (FdU) resistance...Cytotoxic T cell depletion abolished the benefits of UNG depletion in both models. These findings suggest UNG inhibition and/or depletion could enhance antitumor immune response in humans.

Targeting UNG alongside DNA-damaging therapies could disrupt cancer progression. Further studies on BER genes may support personalized treatment approaches in prostate cancer.

The inhibition of uracil DNA glycosylase increased the mutation frequency, and in particular, the frequency of G→A transitions. These results indicated that uracil DNA glycosylase, in addition to APOBEC3, is involved in the untargeted mutation process induced by GO.

These results indicate dysfunction in the base excision repair pathway in AA tumors. Further, these findings reveal how metabolic rewiring in AA PCa drives biological disparities and identifies a targetable axis for cancer therapeutics.