COMBINATORIAL METHODS AND COMPOSITIONS FOR TREATMENT OF MELANOMA

摘要

The present invention provides a rational basis for combining targeted therapies together with selected chemotherapeutics, which does not currently exist for the treatment of melanoma. The present invention is based on the present inventors' discovery that Akt3 regulates apoptosis and V599E B-Raf regulates growth and vascular development in melanoma. Inventors are the fir st to recognize an effective combined targeted therapeutic for treating melanom a. In one embodiment, the invention provides a method for inducing apoptosis in a melanoma tumor cell by reducing Akt3 activity. In yet another embodiment, th e invention provides a method for inducing apoptosis in a melanoma tumor cell comprising contacting a melanoma tumor cell with an agent that reduces Akt3 activity. Consequently, the method provided restores normal apoptotic sensitivity to a melanoma tumor cell, thereby allowing the administration of a lower concentration of chemotherapeutic agents resulting in decreased toxici ty to a patient. The present inventors' contemplate a method for treating a melanoma tumor in a mammal comprising: administering to a melanoma tumor an effective amount of an agent to induce apoptosis; and administering to a melanoma tumor an effective amount of an agent to reduce angiogenesis and ce ll proliferation. Also disclosed herein is a method for treating a melanoma in a mammal comprising: administering to a melanoma tumor in a mammal an effectiv e amount of an agent that reduces Akt3 activity; administering to a melanoma tumor in a mammal an effective amount of an agent that reduces V599E B-Raf activity, thereby treating a melanoma tumor. In another aspect, the inventio n provides a pharmaceutical composition for treating a melanoma tumor comprising: an agent that reduces Akt3 activity; and a carrier.