Experimental prostatic carcinogenesis: molecular targets and therapeutic perspectives

• Grant number: 14/14202-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2014
• End date: October 31, 2016
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Wellerson Rodrigo Scarano
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Robson Francisco Carvalho

Abstract

Prostate cancer is related to the endocrine system and its progression involves changes in estrogen and androgen signaling pathways. Therefore the investigation of drugs that interfere in these pathways creates perspective for discovery of novel therapeutic targets.In this scenario, androgen deprivation has been used as the main treatment for tumor reduction.The antiandrogen abiraterone acetate, a CYP17 inhibitor has been used to treat advanced stages of the disease. However its use can trigger drug resistance mechanisms requiring additional treatments to control disease progression. In this direction the association of this therapy with inhibitors of signaling pathways related to progression of prostate carcinogenesis, such as the PI3K/Akt, appears an alternative strategy for effective treatment of disease.In parallel, studies have investigated the role of estradiol on the etiology of prostate cancer and the use of drugs that modulate estrogen receptors and represent therapeutic strategies against this disease.Recent findings propose that ER² as a possible therapeutic target, however are scarce the researches that explain the mechanisms behind the functions of this receptor. Nowadays, a body of evidences shows the miRNA, small non-coding RNAs, could belinked with the development and progression of several malignancies. Studies that correlate the ER² functions with the miRNA expression during the prostate carcinogenesis are important to improve the knowledge about signaling pathways related to tumor process and create opportunities to find new therapeutic targets.Thus, the aim of this study was to evaluate alternative therapeutic strategies based on modulation of androgen and estrogen signaling pathways for the treatment of prostate cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GONCALVES, BIANCA FACCHIM; PEGORIN DE CAMPOS, SILVANA GISELE; FAVARO, WAGNER JOSE; BRANDT, JOYCE ZALOTTI; PINHO, CRISTIANE FIGUEIREDO; JUSTULIN, LUIS ANTONIO; TABOGA, SEBASTIAO ROBERTO; SCARANO, WELLERSON RODRIGO. Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats. HORMONES & CANCER, v. 9, n. 3, p. 175-187, JUN 2018. (14/14202-7, 13/22604-5)

SALATA, GIOVANNA CASSONE; PINHO, CRISTIANE FIGUEIREDO; DE FREITAS, ANDRE T. A. G.; AQUINO, ARIANA MUSA; JUSTULIN, LUIS ANTONIO; MENDES, LEONARDO OLIVEIRA; GONCALVES, BIANCA F.; DELELLA, FLAVIA KARINA; SCARANO, WELLERSON RODRIGO. Raloxifene decreases cell viability and migratory potential in prostate cancer cells (LNCaP) with GPR30/GPER1 involvement. Journal of Pharmacy and Pharmacology, v. 71, n. 7, p. 1065-1071, JUL 2019. (14/14202-7)