Dipartimento di Scienza e Tecnologia del Farmaco

Descrizione del progetto

Members of other units:

Klaus Pors - Institute of Cancer Therapeutics, Bradford University (UK)

Partners: 

UNITO

Sponsors: 

Description:

Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy and leading cause of cancer mortality in men. At the initial stages, prostate cancer is dependent upon androgens for their growth and hence effectively combated by androgen deprivation therapy (ADT). However, most patients eventually recur with an androgen deprivation-resistant phenotype, referred to as castration-resistant prostate cancer (CRPC), a more aggressive form for which there is no effective therapy presently available. Although the mechanisms of resistance are multi-factorial, the androgen axis still plays a major role in being active even after ADT. The increased expression of enzymes able to facilitate the intratumoral conversion of circulating adrenal androgen precursors to the active AR ligands could be responsible of the CRPC surviving mechanisms. Aldo-keto reductase 1C3 (AKR1C3) is an enzyme that plays a pivotal role in androgen biosynthesis with implication for the development of CRPC, providing AKR1C3 as a clinically-relevant target for drug development. In this project, in collaboration with the Medsynth group of this Dept, the efficacy of novel bioisosteres of flufenamic acid and indomethacin is assessed on AKR1C3 by biochemical and cellular-based assays.  

Techiques and facilities:

• expression and purification of recombinant proteins
• Protein electrophoresis and Immunoassays (western Blot, ELISA)
• UV-Vis, Fluorescence spectroscopy
• Enzymatic assays
• Prostate cancer cell culture

Cytotoxicity assays on cell cultures (sulforhodamine B or MTT) 

Keywords: Androgen pathway, prostate cancer, AKR1C3, Androgen receptor, Inhibitors, Antitumoral activity, Enzymatic activity, proliferation

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