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Alternative drugs for the treatment of prostate cancer

A major problem of hormonal chemotherapy in prostate cancer is the development of drug resistance. An EU-funded project has been developing new alternative therapeutics for the treatment.
Alternative drugs for the treatment of prostate cancer
Prostate cancer is one of the most prevalent cancers in the male population. Patients diagnosed with early-stage prostate cancer have excellent prognosis and can survive for many years through a chemotherapeutic anti-hormonal treatment regimen. One of the existing anti-hormonal treatments for prostate cancer involves ligand-binding pocket (LBP) antiandrogens that bind to AR in the LBP mimicking the mode of action of androgen.

Moreover, prolonged use of these drugs often results in the disease becoming hormone-refractory. The hormone-resistant cancer is frequently metastatic and almost invariably fatal. Current treatments require high dosing and show significant side-effects. The aim of this project was to develop drugs that combat prostate cancer in an alternative way.

In the present project computational rational design allowed the identification of 15 new hits by combining virtual screening, similarity and docking techniques. All these compounds have shown alternative, non-LBP, anti-androgen activity. Structural analysis of the new family of compounds (diarylhydrazides) has been performed to determine its most relevant features.

The results of this project offer an important general input for the field of rational design of new therapeutics for the treatment of drug-resistant cancer.

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