Therapeutic potential of calcitriol, the active metabolite of Vitamin D, for the treatment of Leydig cell tumors.

LAZZATI, JM; PIGNATARO, OP; ABIUSO, AMB; BELGOROSKY, A; MONDILLO, C; VARELA, ML; BESIO MORENO, M; BERENSZTEIN, E

Mar del Plata

Congreso; Reunión anual de Sociedades de Biocencia: SAIC-SAFE-SAB-SAP; 2019

Sociedad Argentina de Investigación Clínica

Leydig cell tumors (TCL) are endocrine tumors from the testicular interstitium. They present a great complexity of associated clinical anomalies, due to hormonal alterations. Classic treatment is orchiectomy or, if possible, removal of the affected area. Regardless, patients must be monitored indefinitely since TCL metastases even 9 years after primary tumor removal with an average survival of 2 years, due to not responding to chemo/radiotherapy.Epidemiological studies strongly support a relationship between vitamin D deficiency and multiple pathologies, including cancer. In this sense, the potential therapeutic role of calcitriol (active molecule of vitamin D) was described for several types of tumors. Our previous reports showed calcitriol is able to inhibit proliferation and steroidogenesis as well as modulate the histaminergic system in tumoral Leydig cells (TLC). Specifically, it enhances the histamine H4 receptor (HRH4) expression, which is a promising therapeutic target for the treatment of autoimmune diseases, allergy, and cancer. We reported specific HRH4 agonist VUF8430 (VUF), is capable of inhibiting steroidogenesis, proliferation, and pro-angiogenic capacity of TLC. This work evaluates using murine in vivo models and samples of pediatric pathological testis, the interaction between calcitriol and HRH4 agonist, as well as the potential use of a combination as a strategy in the treatment of LCT.In vitro results showed calcitriol treatment boosts HRH4 in TLC. Our in vivo showed calcitriol treated mice tumors were in 61.7% smaller and VUF treated were 48.6% smaller. Nevertheless, simultaneous treatment produced only a 30.2% smaller tumor. We were able to conclude both calcitriol and VUF are good agents for slowing tumor growth. However together they didn?t show a synergic response. We have yet to determine if a different administration of drugs could result in a better outcome. Both calcitriol and VUF are promising therapeutic options for LCT treatment.