Combinations of agents that have a synergistic effect for the treatment of a tumor are disclosed herein. These combinations of agents can be used to treat tumors, wherein the cells of the cancer express a mutated BRAF. Methods are disclosed for treating a subject diagnosed with a tumor that expresses a mutated BRAF. The methods include administering to the subject (1) a therapeutically effective amount of an antibody or antigen binding fragment thereof that specifically binds high molecular weight melanoma associated antigen (HMW-MAA), also known as CSPG4; and (2) a therapeutically effective amount of a BRAF inhibitor. In some embodiments, the tumor is melanoma. In some embodiments the method includes selecting a subject with primary or secondary resistance to a BRAF inhibitor. In further embodiments, treating the tumor comprises decreasing the metastasis of the tumor. In additional embodiments, the BRAF inhibitor comprises PLX4032 or PLX4720.
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