Peter Hersey1. 1. Oncology and Immunology Unit, David Maddison Clinical Sciences Building, Newcastle, New South Wales, Australia. Peter.Hersey@newcastle.edu.au
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: Delphine Lamoral-Theys; Anna Andolfi; Gwendoline Van Goietsenoven; Alessio Cimmino; Benjamin Le Calvé; Nathalie Wauthoz; Véronique Mégalizzi; Thierry Gras; Céline Bruyère; Jacques Dubois; Véronique Mathieu; Alexander Kornienko; Robert Kiss; Antonio Evidente Journal: J Med Chem Date: 2009-10-22 Impact factor: 7.446