Apoptosis and melanoma: how new insights are effecting the development of new therapies for melanoma.
OBJECTIVE
Melanoma has proven resistant to most available chemotherapy and immunotherapy. Despite a range of different biochemical targets, most agents kill cancer cells by induction of apoptosis.


RESULTS
Investigation of this process has provided insights into the resistance mechanisms in cancer cells and to development of a range of new agents that target apoptosis pathways. These include agents which inhibit antiapoptotic B cell lymphoma-2 family proteins and inhibitor of apoptosis proteins. In addition, a range of signal pathway inhibitors have become available that are able to inhibit signal pathways known to be associated with resistance to apoptosis.


CONCLUSIONS
Evaluation of most of these reagents are at a preclinical level but studies on some pathway inhibitors have passed from phase II into phase III studies. Similarly, evaluation of antisense reagents are at an advanced stage. These early trials show much promise and suggest this approach to development of new therapies will lead to much needed advances in treatment of this disease.
Hersey
Peter
P
Oncology and Immunology Unit, David Maddison Clinical Sciences Building, Newcastle, New South Wales, Australia. Peter.Hersey@newcastle.edu.au
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases