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Glutamate Carboxypeptidase II as a Drug Target and a Molecular Address for Cancer Treatment
Knedlík, Tomáš ; Konvalinka, Jan (advisor) ; Stiborová, Marie (referee) ; Souček, Pavel (referee)
Glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA), is a membrane metallopeptidase overexpressed on most prostate cancer cells. Additionally, GCPII also attracted neurologists' attention because it cleaves neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG). Since NAAG exhibits neuroprotective effects, GCPII may participate in a number of brain disorders, which were shown to be ameliorated by GCPII selective inhibitors. Therefore, GCPII has become a promising target for imaging and prostate cancer targeted therapy as well as therapy of neuronal disorders. Globally, prostate cancer represents the second most prevalent cancer in men. With the age, most men will develop prostate cancer. However, prostate tumors are life threatening only if they escape from the prostate itself and start to spread to other tissues. Therefore, considerable efforts have been made to discover tumors earlier at more curable stages as well as to target aggressive metastatic cancers that have already invaded other tissues and become resistant to the standard treatment. Since patients undergoing a conventional therapy (a combination of chemotherapy and surgery) suffer from severe side effects, more effective ways of treatment are being searched for. Novel approaches include selective...
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