Cancer Treat Rev 2018 Dec 20;71:19-31. Epub 2018 Sep 20.
Laboratory of Experimental and Molecular Neuroimaging (LEMNI), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Drive, Grant S-047, Stanford, CA 94305, USA. Electronic address:
p53 is a transcription factor that activates numerous genes involved in essential maintenance of genetic stability. P53 is the most frequently mutated gene in human cancer. One third of these mutations are structural, resulting in mutant p53 with a disrupted protein conformation. Here we review current progress in a relatively underexplored aspect of p53-targeted drug development, that is, strategies to reactivate wild-type function of misfolded mutant p53. Unfortunately, most p53-targeted drugs are still at early stages of development and many of them are progressing slowly toward clinical implementation. Significant challenges need to be addressed before clinical translation of new anti-misfolding p53-targeted drugs.