Τόμος 27 (2009) – Τεύχος 1 – Άρθρο 32 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 27 (2009) – Issue 1– Article 32 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Ογκοκατασταλτική Πρωτεΐνη p53: Προοπτικές Εφαρμογής στη Θεραπεία του Καρκίνου

Tumor Suppressor p53 Protein: Perspectives of Cancer Therapy

Ελληνικά – Greek

Άρθρο

Article

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The aim of this work is to present the two major anti-cancer therapeutic strategies targeting p53: p53 protein reactivation leading to apoptosis of tumor cells, and selective inhibition of p53 in normal tissues, targeting to reducing side effects of conventional chemotherapy and radiotherapy. In the vast majority of tumors, inactivation of p53 is related with point mutations or with abnormal expression of proteins regulating p53, like MDM2, MDMX and E6, and not with loss of gene. Thus, p53 may be reactivated either by genetic manipulation or by small molecules that target its interaction with inhibitory proteins or restore the functionality of mutant p53. A number of compounds have been tried, such as 1,2-benzodiazopine-2-one, chalcones, quinacrine, PNC-28 and nutlins, which inhibit binding of MDM2 to p53 or inhibit the NF-kB-dependent suppression of p53, and result to p53 protein reactivation, and death of tumor cells, without affecting the growth of normal cells. P53 inhibitors such as PFT-a are used to reduce the toxic effects of conventional cancer treatment, due to apoptotic activity of p53 in hematopoietic and lymphopoietic sites, small intestine and hair follicles. P53 inhibitors could be used only in p53-deficient tumors and are highly selective for normal tissues.