Phase 1 trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study

摘要

Background. p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G(2)/M. We conducted a phase 1 study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children.