Novel Therapeutics for Melanoma

Nagashree Seetharamu; Patrick A Ott; Anna C Pavlick


Expert Rev Anticancer Ther. 2009;9(6):839-849. 

In This Article

Expert Commentary

Understanding the molecular biology of melanoma and unraveling of several signaling pathways over the last few years, as well as advances in immunology have led to the development of a number of novel therapeutic targets in melanoma. Nevertheless, therapy for advanced melanoma remains an enormous challenge. None of the aforementioned novel and promising strategies have yet shown an OS benefit compared with standard therapy in a randomized Phase III setting. Some of the novel therapeutics are simply not yet developed sufficiently to have reached this stage of clinical testing, but others have failed (i.e., sorafenib in combination with chemotherapy in first and second line, oblimersen combined with dacarbazine in unselected stage IV melanoma patients and tremelimumab as a single agent in the first-line setting). For some of the new immune-regulatory antibodies described above, standard RECIST criteria might not be adequate for the assessment of clinical response. It has been suggested that potential clinical activity of immunological checkpoint blockade with tremelimumab might have been missed in Phase III testing owing to the failure to recognize the fact that immune-related response criteria are needed for response assessment. Clinical trials combining agents with different targets and requiring tissue biopsies to assess the impact of these agents on pathways and biomarkers are vital for the advancement of the treatment of this disease. Identifying genetic signatures of tumors in responding patients will assist in the future selection of therapeutic options for patients once these unique features are characterized.


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