Synthesis of a potential inhibitor of acid ceramidases targeting the prostate cancer treatment

• Grant number: 22/12326-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: March 31, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Daniel Fábio Kawano
• Grantee: Giovana da Costa Venancio
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 23/13541-1 - Biological characterization of a novel potential acid ceramidase inhibitor in acute myeloid leukemia cells, BE.EP.IC

Abstract

Prostate cancer represents the second most frequent type of cancer among men, with the development of metastases being the main cause of death associated with it. In this sense, the involvement of adjacent lymph nodes, liver, lungs and, especially, bones is common, with 9 out of 10 patients with metastatic prostate cancer manifesting bone tissue involvement. Although androgen castration therapy is effective and safe in the early stages of the disease, it can induce repopulation of the tumor mass with resistant cells, as well as their metastatic derivatives. In these cases, chemotherapy with docetaxel or mitoxantrone can be used, but the median survival of these patients does not reach 18 months. Interestingly, the inhibition of acid ceramidases makes it possible to sensitize prostate cancer cells to chemotherapy and radiotherapy, thus reducing tumor growth and preventing cancer recurrence. In this context, this research project proposes the development of a covalent inhibitor of this enzyme that potentially has the necessary metabolic stability to be used orally in the treatment of prostate cancer, ideal characteristics that none of the drugs currently marketed have.