In vitro evidence for a new therapeutic approach in renal cell carcinoma.
OBJECTIVE
Renal cell carcinoma (RCC) is the most lethal among the common urologic malignancies, comprising 3% of all human neoplasias; approximately 40% of patients eventually die of cancer progression. One third of patients who present with metastatic disease and up to 40% 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.


CONCLUSIONS
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.
Pittoggi
Carmine
C
SBGSA, Italian National Institute of Health, Rome, Italy. carminepittoggi@hotmail.com
Martis
Gianni
G
Mastrangeli
Giorgia
G
Mastrangeli
Bruno
B
Spadafora
Corrado
C
D000480:Alkynes; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003521:Cyclopropanes; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019829:Nevirapine / Q000627:therapeutic use*; D012313:RNA / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000480:Alkynes; D000970:Antineoplastic Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D012313:RNA; D019829:Nevirapine; C098320:efavirenz