BIOL 467 Lecture Notes - Lecture 18: Apoptosome, P53, Glioblastoma Multiforme
Document Summary
P53 inactivation = evade senescence, most mutated gene in cancers. Ca(cid:374)(cid:272)ers ha(cid:448)e (cid:1005)(cid:1004)(cid:1004)(cid:859)s (cid:1005)(cid:1004)(cid:1004)(cid:1004)(cid:859)s of (cid:373)utatio(cid:374)s! Ras mutations are common in pancreatic cancers, but not in glioblastomas. If the tumor has p53 intact, many of the drugs will work very well on those cancers. Drugs that stimulate p53 in response to dna damage have high success rates if p53 is intact. But p53 is one of the most frequently mutated genes in cancers! Drugs that target anti-apoptotic regulators, such as bcl2, or ligands/receptors of extrinsic death. Target downstream of p53 so cells no longer require functional p53 to stimulate apoptosis pathways are in clinical trials. Slide 4 extrinsic and intrinsic extrinsic: external cues that tell the cell it has to die, or you stimulate your suicide (intrinsic) largely through p53, to stimulate formation of apoptosome, caspase 9, then downstream caspases. Extrinsic pathway is a target for drug development, but so is targeting intrinsic pathway.
