Recombinant Human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Selectively Induces Apoptosis in Malignant Melanoma

Skin cancer is among the most commonly-diagnosed cancers with malignant melanoma being associated with the highest rate of metastasis and death. In its early stage, melanoma is easily cured, but the prognosis associated with metastatic malignant melanoma remains very poor and is one of the most treatment-refractory malignancies. This work was undertaken to assess the effectiveness and safety of recombinant human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhTRAIL) as a potential therapeutic for malignant melanoma. rhTRAIL is the optimized version of the naturally-occurring death-ligand TRAIL. TRAIL shows cancer cell specificity through its innate ability to induce apoptosis in a broad range of transformed human cells while showing no toxicity toward normal healthy cells. Utilizing malignant melanoma A375 cells and normal human melanocytes, the efficacy and safety of rhTRAIL was determined in vitro and in vivo through nude mice A375 xenografts. rhTRAIL induced significant levels of apoptosis in malignant melanoma cells in vitro and at the same time did not induce apoptosis in non-transformed melanocytes. rhTRAIL showed remarkable in vivo potency and was able to inhibit the growth of established melanoma tumors while showing no toxicity towards the mice model. These data suggest that rhTRAIL is a valid candidate for the treatment of malignant melanoma, displaying significant anti-tumor activity with sustainably less negative side effects than traditional therapies.