Transcriptional regulators in human hepatocarcinogenesis
Identification of key integrators using functional genomics
v-myc avian myelocytomatosis viral oncogene homolog (c-Myc)
v-myb myeloblastosis viral oncogene homolog (avian)-like 2 (b-Myb)
- Calvisi D.F.
- Simile M.M.
- Ladu S.
- Frau M.
- Evert M.
- Tomasi M.L.
- et al.
- Calvisi D.F.
- Simile M.M.
- Ladu S.
- Frau M.
- Evert M.
- Tomasi M.L.
- et al.
Activator protein-1 (AP-1)
Hypoxia-inducible factor-1 (HIF-1)
- Simon F.
- Bockhorn M.
- Praha C.
- Baba H.A.
- Broelsch C.E.
- Frilling A.
- et al.
E2F transcription factors
Homeobox (HOX) proteins
Implications for targeted therapy
- (1)Although global inhibition of transcription factors may cause acceptable unwanted effects [], tumor cell-specific targeting is preferable. Systemic approaches might cause severe side effects under specific physiological conditions (e.g., regeneration).
- (2)At least in some cases, targeting approaches have to discriminate between structurally related proteins, since different family members facilitate distinct biological features (e.g., AP-1 subunits). Blocking entire protein families may lead to uncontrolled and even opposite effects.
- (3)Transcriptional regulators lack enzymatic activity; thus, protein-directed inhibitors may have to disturb large surface protein/protein or protein/DNA interaction structures (e.g., c-Myc/Max heterodimers) posing additional challenge, e.g., on lead substance optimization.
Chemical compounds targeting transcription factor activity and expression
- Coleman D.R.t.
- Ren Z.
- Mandal P.K.
- Cameron A.G.
- Dyer G.A.
- Muranjan S.
- et al.
Gene therapeutic approaches
Conflict of interest
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