TY - JOUR
T1 - Antitumor Effects of PRIMA-1 and PRIMA-1Met (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?
AU - Menichini, Paola
AU - Monti, Paola
AU - Speciale, Andrea
AU - Cutrona, Giovanna
AU - Matis, Serena
AU - Fais, Franco
AU - Taiana, Elisa
AU - Neri, Antonino
AU - Bomben, Riccardo
AU - Gentile, Massimo
AU - Gattei, Valter
AU - Ferrarini, Manlio
AU - Morabito, Fortunato
AU - Fronza, Gilberto
N1 - Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/1/7
Y1 - 2021/1/7
N2 - Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.
AB - Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.
KW - CLL
KW - hematological malignancies
KW - leukemia
KW - mutant P53
KW - PRIMA-1/APR246
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U2 - 10.3390/cells10010098
DO - 10.3390/cells10010098
M3 - Review article
C2 - 33430525
AN - SCOPUS:85099897721
VL - 10
SP - 98
JO - Cells
JF - Cells
SN - 2073-4409
IS - 1
ER -