Targeting histones and proteasomes: New strategies for the treatment of lymphoma Journal Article
| Authors: | O'Connor, O. A. |
| Article Title: | Targeting histones and proteasomes: New strategies for the treatment of lymphoma |
| Abstract: | Our ever-increasing understanding of cancer cell biology has begun to provide a variety of new, and potentially drugable targets for the treatment of many forms of cancer. Nowhere else is this more apparent than in the treatment of the lymphomas. A rapidly emerging experience in gene expression profiling has begun to suggest that we can define different subtypes of lymphoma on the basis of unique molecular signatures. These signatures can define important signaling pathways that may help account for the biology of different subsets of lymphoma, and are teaching us that the lymphomas are truly a heterogeneous set of diseases. What remains equally as interesting is the idea that empiric observations of novel targeted drugs in select subtypes of lymphoma can teach us much about the biology of different lymphomas. A priori assumptions about the anticipated activity of novel targeted agents in select subtypes of lymphoma have been turned upside down. Two pathways that have emerged recently as potentially important targets for new agents in lymphoma include the ubiquitin proteasome pathway and the biochemical reactions that control histone acetylation. New classes of drugs that affect these targets, such as bortezomib, depsipeptide, suberoylanilide hydroxamic acid, and a host of other compounds, though affecting a unique target in the cell, are associated with a remarkable panoply of different downstream biologic effects. In this article, we will review some of the prevailing theories about how these novel targeted drugs affect lymphoma biology, and how these compounds are changing the face of lymphoma therapy. © 2005 by American Society of Clinical Oncology. |
| Keywords: | survival; treatment outcome; survival analysis; unclassified drug; genetics; histone deacetylase inhibitor; clinical trial; drug activity; fatigue; mortality; review; advanced cancer; diarrhea; disease classification; antineoplastic agents; drug approval; drug targeting; comparative study; follow up; follow-up studies; antineoplastic agent; ubiquitin; anorexia; metabolism; bortezomib; proteasome; controlled clinical trial; mantle cell lymphoma; multiple myeloma; proteasome endopeptidase complex; gene expression; randomized controlled trial; thrombocytopenia; dehydration; immunoglobulin enhancer binding protein; food and drug administration; drug effect; pathology; cancer therapy; hodgkin disease; risk assessment; drug delivery systems; hospitalization; cutaneous t cell lymphoma; nonhodgkin lymphoma; severity of illness index; drug mechanism; randomized controlled trials; lymphoma, non-hodgkin; histone; protein p27; lymphoma; vorinostat; protein bcl 6; cyclin dependent kinase inhibitor; histones; drug delivery system; valproic acid; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; trichostatin a; lymphoma, mantle-cell; depsipeptide; benzamide derivative; nicotinamide; hydroxamic acid derivative; fr 901228; lactacystin; 4 phenylbuterate; tetrapeptide |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 23 |
| Issue: | 26 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2005-09-10 |
| Start Page: | 6429 |
| End Page: | 6436 |
| Language: | English |
| DOI: | 10.1200/jco.2005.05.014 |
| PUBMED: | 16155030 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus" |
