Exploiting BH3 only protein function for effective cancer therapy.
Failure to induce tumour selective, efficient cell killing is a major problem underlying the limitations of conventional cytotoxic chemotherapy. Greater understanding of the downstream death inducing signalling pathways and how they are regulated in the drug resistant setting is crucial for improvement of survival in most solid cancers. Here we review the role played by BH3 only proteins in mediating cell death through BAX and BAK, and how this knowledge has lead to a new generation of targeted agents with promising cancer cell killing efficacy.
Fennell
Dean A
DA
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland. d.fennell@qub.ac.uk
Chacko
Alex
A
D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000502:physiology* / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011518:Proto-Oncogene Proteins / Q000502:physiology* / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000502:physiology* / Q000627:therapeutic use*
C474007:Bax protein (53-86); D026901:Membrane Transport Proteins; D010446:Peptide Fragments; D061988:Proteasome Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c