Targeting the RB-pathway in cancer therapy.
The RB-pathway, consisting of inhibitors and activators of cyclin-dependent kinases, the retinoblastoma tumor suppressor (RB), and the E2F-family of transcription factors, plays critical roles in the regulation of cell cycle progression and cell death. Components of this pathway, particularly p16Ink4a, cyclin D1, and RB, are frequently altered in sporadic human cancers to promote deregulated cellular proliferation. The consistent disruption of the RB-pathway in human cancers raises the possibility of exploiting tumor-specific RB-pathway defects to improve the efficacy of current therapies and to develop new therapeutic strategies. This article discusses how the RB-pathway status impacts the cellular responses to cytotoxic, cytostatic, and hormone therapies, and how the components of the RB-pathway may be directly targeted to treat cancer.
Knudsen
Erik S
ES
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Wang
Jean Y J
JY
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004249:DNA Damage; D050704:E2F4 Transcription Factor / Q000037:antagonists & inhibitors*; D047628:Estrogen Receptor alpha; D006801:Humans; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D050704:E2F4 Transcription Factor; D047628:Estrogen Receptor alpha; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases