Therapeutic targeting of apoptosis pathways in cancer.
OBJECTIVE
Anti-apoptotic mechanisms contribute to the development of cancer and the resistance of cancer cells to antitumor therapies. This review focuses on the progress towards clinical application of therapies that directly modulate the apoptosis pathways.


RESULTS
A growing understanding of the mechanisms that control apoptosis has generated a number of strategies for modulating apoptotic pathways, including activation of death receptors and neutralization of anti-apoptotic proteins. Striking antitumor efficacy has been achieved in preclinical cancer models. To date, early-phase testing has not yet established the clinical utility of these strategies.


CONCLUSIONS
There is every reason to be optimistic that the wealth of knowledge about the molecular controls of apoptosis will eventually be translated into new clinical therapies for cancer. It is likely that the optimum utility of these pro-apoptotic therapies will be in combination with other treatment modalities, and careful patient selection will be necessary.
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David S
DS
Ziegler
Andrew L
AL
Kung
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D053218:Receptors, Death Domain / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53