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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2011

Open Access 01-12-2011 | Review

Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

Authors: Yuan Yuan, Yu-Min Liao, Chung-Tsen Hsueh, Hamid R Mirshahidi

Published in: Journal of Hematology & Oncology | Issue 1/2011

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Abstract

We reviewed preclinical data and clinical development of MDM2 (murine double minute 2), ALK (anaplastic lymphoma kinase) and PARP (poly [ADP-ribose] polymerase) inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC). Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation.
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Metadata
Title
Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP
Authors
Yuan Yuan
Yu-Min Liao
Chung-Tsen Hsueh
Hamid R Mirshahidi
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2011
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-4-16

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