Delivery of cell cycle genes to block astrocytoma growth.
Current therapies for glioblastoma multiforme are ineffective. Therefore, novel therapies that target specific differences between normal and malignant cells are urgently needed. Abnormalities of cell-cycle related genes are a common feature of cancer in general and astrocytic tumors in particular. The role of these proteins is to help to regulate cell proliferation, differentiation and apoptosis. Restoring wild-type activity of critical regulators of the cell cycle to astrocytic tumors generally results in modification of the growth properties, and often the viability, of the cancer cells. Transfer of p53 induces growth arrest and, more importantly, apoptosis. Restoration of the Rb pathway results in either reversible growth arrest or senescence. Expression of E2F-1 induces transient increase of proliferation followed by massive apoptosis. Overexpression of MMAC/PTEN arrests cell cycle progression in G1 and promotes anoikis. Current knowledge of the functions of these cell-cycle controllers can be used to design small peptides and drugs to induce cell-cycle related anti-cancer effect. Inactivation of the p53 and Rb pathways in cancer cells is also being used to engineer mutant viruses that are able to replicate exclusively in cancer cells.
Fueyo
J
J
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Gomez-Manzano
C
C
Liu
T J
TJ
Yung
W K
WK
D000818:Animals; D001254:Astrocytoma / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D018014:Gene Transfer Techniques; D016158:Genes, p53; D006801:Humans; D005810:Multigene Family; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human