PRIMA-1 and PRIMA-1 (APR-246): From Mutant/Wild Type P53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2017 Dec 21

PMID 29258181

Citations 65

Authors

Anne Perdrix

Ahmad Najem

Sven Saussez

Ahmad Awada

Fabrice Journe

Ghanem Ghanem

Mohammad Krayem

Affiliations

Soon will be listed here.

Abstract

p53 protects cells from genetic assaults by triggering cell-cycle arrest and apoptosis. Inactivation of p53 pathway is found in the vast majority of human cancers often due to somatic missense mutations in TP53 or to an excessive degradation of the protein. Accordingly, reactivation of p53 appears as a quite promising pharmacological approach and, effectively, several attempts have been made in that sense. The most widely investigated compounds for this purpose are PRIMA-1 (p53 reactivation and induction of massive apoptosis )and PRIMA-1 (APR-246), that are at an advanced stage of development, with several clinical trials in progress. Based on publications referenced in PubMed since 2002, here we review the reported effects of these compounds on cancer cells, with a specific focus on their ability of p53 reactivation, an overview of their unexpected anti-cancer effects, and a presentation of the investigated drug combinations.

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