Phase I 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 | Zendy

Rishi Lulla | Zendy; Stewart Goldman | Zendy; Tohru Yamada | Zendy; Craig W. Beattie | Zendy; Linda R. Bressler | Zendy; Michael Pacini | Zendy; Ian F. Pollack | Zendy; Paul G. Fisher | Zendy; Roger J. Packer | Zendy; Ira J. Dunkel | Zendy; Girish Dhall | Zendy; Shengjie Wu | Zendy; Arzu Onar | Zendy; James M. Boyett | Zendy; Maryam Fouladi | Zendy

Open Access

Phase I 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

Author(s) -

Rishi Lulla,

Stewart Goldman,

Tohru Yamada,

Craig W. Beattie,

Linda R. Bressler,

Michael Pacini,

Ian F. Pollack,

Paul G. Fisher,

Roger J. Packer,

Ira J. Dunkel,

Girish Dhall,

Shengjie Wu,

Arzu Onar,

James M. Boyett,

Maryam Fouladi

Publication year - 2016

Publication title -

neuro-oncology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 4.005

H-Index - 125

eISSN - 1523-5866

pISSN - 1522-8517

DOI - 10.1093/neuonc/now047

Subject(s) - adverse effect , medicine , toxicity , cell cycle , pharmacokinetics , cancer , chemotherapy , cell cycle checkpoint , immunohistochemistry , oncology , pharmacology

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 G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children.

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