Histone deacetylase inhibitors in malignant pleural mesothelioma: Preclinical rationale and clinical trials Journal Article
| Authors: | Paik, P. K.; Krug, L. M. |
| Article Title: | Histone deacetylase inhibitors in malignant pleural mesothelioma: Preclinical rationale and clinical trials |
| Abstract: | Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer of the mesothelium with only a limited range of treatment options that are largely ineffective in improving survival. Recent efforts have turned toward the analysis of specific, dysregulated biologic pathways for insight into new treatment targets. Epigenetic regulation of tumor suppressor genes through chromatin condensation and decondensation has emerged as an important mechanism that leads to tumorogenesis. A family of histone acetyltransferases and deacetylases regulates this balance, with the latter facilitating chromatin condensation, thus preventing gene transcription, resulting in the loss of heterozygosity of tumor suppressors. Inhibition of this process, coupled with a similar inhibition of nonhistone protein deacetylation, ultimately leads to the promotion of apoptosis, cell cycle arrest, and inhibition of angiogenesis. An increasing amount of preclinical data highlighting the effectiveness of histone deacetylase inhibition in MPM cell lines and mouse xenograft models has led to a number of early phase clinical trials in patients with MPM. The results of these efforts have led to a multicenter, randomized, placebo-controlled phase III study of the histone deacetylase inhibitor vorinostat in patients with advanced MPM, offering hope for a new and effective therapy in patients with this disease. © 2010 by the International Association for the Study of Lung Cancer. |
| Keywords: | cancer chemotherapy; protein expression; treatment response; overall survival; histone deacetylase inhibitor; clinical trial; fatigue; review; cisplatin; placebo; monotherapy; side effect; solid tumor; antineoplastic agents; clinical trials as topic; gemcitabine; paclitaxel; outcome assessment; animals; mice; carboplatin; progression free survival; quality of life; apoptosis; controlled clinical trial; bone marrow suppression; nausea; randomized controlled trial; vomiting; dehydration; genetic transcription; caspase 3; cancer cell culture; cytotoxicity; drug potency; drug evaluation, preclinical; cancer therapy; carcinogenesis; cancer inhibition; tumor suppressor gene; clinical study; drug mechanism; xenograft; epigenetics; multicenter study; transcription factor sp1; pleura mesothelioma; mesothelioma; vorinostat; histone deacetylase inhibitors; hydroxamic acids; reactive oxygen metabolite; cell cycle arrest; flavopiridol; heterozygosity loss; lung function; oncogene c myb; pemetrexed; pleural neoplasms; hematologic disease; lipocortin 5; valproic acid; belinostat; nephroblastoma; depsipeptide; protein p300; pleural mesothelioma; caspase 7; chromatin condensation; drug acetylation; drug evaluation |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 5 |
| Issue: | 2 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2010-02-01 |
| Start Page: | 275 |
| End Page: | 279 |
| Language: | English |
| DOI: | 10.1097/JTO.0b013e3181c5e366 |
| PUBMED: | 20035240 |
| PROVIDER: | scopus |
| PMCID: | PMC4052955 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "Source: Scopus" |
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