In vitro evidence for a new therapeutic approach in renal cell carcinoma

ABSTRACT

PURPOSE: Renal cell carcinoma (RCC) is the most lethal among the common urologic malignancies, comprising 3 percent of all human neoplasias; approximately 40 percent of patients eventually die of cancer progression. One third of patients who present with metastatic disease and up to 40 percent treated for localized disease generally experience recurrence. RCCs are characterized by high resistance to chemo-, radio- and immunotherapy. We recently discovered an endogenous enzymatic activity, which is particularly expressed in tumorigenic cell, endogenous non-telomerase reverse transcriptase (RT) of retrotrasposon / retroviral origin, as a specific target to induce proliferation arrest in a number of human carcinogenesis in vitro culture cell lines. METHODS: To address this possibility, we have employed RCC primary cell culture testing pharmacological inhibition, in vitro, by two characterized non nucleosidic RT inhibitors, nevirapine and efavirenz; next, we assessed morphological effects and analyzed putative modulation on gene expression profile. RESULTS: Both treatments reduced cell proliferation rate and induced morphological differentiation and gene expression reprogramming in different RCC analyzed tumor biomarkers. CONCLUSION: In this study we describe a new potential therapeutic approach to obtain considerable future benefits in renal carcinoma cure and attempt to establish a new possible pharmacological therapy based on oral drugs administration in renal RCC treatment.