TitleThe theoretical basis of transcriptional therapy of cancer: can it be put into practice?
Publication TypeJournal Article
Year of Publication2005
AuthorsMelnick, Ari M., Adelson Kerin, and Licht Jonathan D.
JournalJ Clin Oncol
Date Published2005 Jun 10
KeywordsAnimals, DNA Methylation, Forecasting, Gene Silencing, Humans, Neoplasms, Promoter Regions, Genetic, Transcription, Genetic

<p>Aberrant gene silencing is a frequent event in cancer and plays a critical role in the molecular pathogenesis of malignant transformation. The two major mechanisms of silencing in cancer include transcriptional repression by mutated or aberrantly expressed transcription factors, and aberrant epigenetic silencing by hypermethylation of tumor suppressor or DNA repair-related genes. Both of these mechanisms require the activities of multiprotein chromatin remodeling and modifying machines, several of which may be mutated in cancer. The end result is genetic reprogramming of cells to express combinations of genes that confer the neoplastic phenotype. Recent discoveries in transcriptional biochemistry and gene regulation indicate that therapeutic agents can be engineered to specifically target these mechanisms. We provide a framework for the clinical or translational scientist to consider how such drugs might be developed and what their impact might be on restoring cells to normal genetic programming.</p>

Alternate JournalJ Clin Oncol
PubMed ID15867201
Grant ListR01 CA59936 / CA / NCI NIH HHS / United States
R01 CA99982 / CA / NCI NIH HHS / United States