International Journal of Cancer and Oncology

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. Received Date: October 28, 2016 Accepted Date: January 10, 2017 Published Date: January 17, 2017 Citation: Kalafatis, M., et al. Recombinant Human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Selectively Induces Apoptosis in Malignant Melanoma. (2017) Int J Cancer Oncol 4(1): 18. DOI: 10.15436/2377-0902.17.1191 Kalafatis, M., et al. New therapeutic strategies are needed to improve the treatment outcome and survival of malignant melanoma patients. Several members of the Tumor Necrosis Factor (TNF) family, including FasL, TNF-α and TNF-Related Apoptosis-Inducing Ligand (TRAIL), robustly induce apoptosis in transformed cancer cells[5]. However, the therapeutic potential of FasL and TNF-α is hindered by their toxicity upon systemic administration. In contrast, TRAIL selectively induces apoptosis in cancer cells. Even at supraphysiological concentrations, TRAIL shows minimal toxicity to healthy non-transformed cells[6,7]. TRAIL acts as a pro-apoptotic ligand through its interactions with extracellular death receptors (DR) DR4 and DR5[8]. Bind-