title: Signal-dependent regulation of gene expression as a target for cancer treatment: inhibiting p38alpha in colorectal tumors.
abstract: In the last year, several evidences indicated that pharmacological manipulation of relevant signaling pathways could selectively affect gene expression to influence cell fate. These findings render of extreme importance the elucidation of how external stimuli are transduced to mediate chromatin modifications, resulting in a permissive or repressive environment for gene expression. These signaling cascades activate or repress the function of chromatin binding proteins that represent attractive pharmacological targets for human diseases. Actually, the closer the target is to chromatin, the more the transcriptional effect will be selective. Recent studies suggest that pharmacological manipulation of signaling pathways to modulate cell fate is indeed possible and that chromatin-associated kinases could represent an optimal target. The p38 MAPK is the prototype of this class of enzymes and its central role in the transcription process is evolutionary conserved. In this review we will focus on the possibility to inhibit p38alpha in colorectal cancer to arrest tumor progression and induce autophagic cell death.
authors.affiliation: Laboratory of Signal-dependent Transcription, Department of Translational Pharmacology (DTP), Consorzio Mario Negri Sud, Via Nazionale 8/A, 66030 Santa Maria Imbaro (Chieti), Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Chiacchiera
authors.forename: Cristiano
authors.initials: C
authors.lastname: Simone
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001343:Autophagy; D002843:Chromatin / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D048308:Mitogen-Activated Protein Kinase 14