title: Antiproteasomal agents in rectal cancer.
abstract: Colorectal cancer (CRC) is a prevalent and highly morbid condition. An improved understanding of the molecular pathogenesis of CRC in recent years has led to novel therapies complementing traditional chemotherapy, radiotherapy, and surgery. As in other cancers, it has become clear that the ubiquitin-proteasome system represents important cellular machinery that plays a complex role in the carcinogenesis of CRC, and may be a promising target for modulation in the treatment of CRC. In particular, there has been promise in targeting nuclear factor-κB and cell-cycle pathways in CRC through proteasome inhibition. Proteasome inhibition may be an important means of sensitizing cancers to traditional chemotherapy and radiotherapy through these pathways. In this review, we outline the basic science of the ubiquitin-proteasome system in CRC pathogenesis, highlight the use of proteasome inhibitors in cancers other than CRCs, and weigh the accumulating evidence and data, both preclinical and clinical, for the use of proteasome inhibition in CRC. Furthermore, we review the emerging evidence of proteasome inhibition as a possible radiosensitizing agent in rectal cancer and elucidate some possible future directions for this novel therapeutic option.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Department of Surgery, Boston, MA 02114, USA.
authors.forename: Claudius
authors.initials: C
authors.lastname: Conrad
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Podolsky
authors.forename: James C
authors.initials: JC
authors.lastname: Cusack
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D020360:Neoadjuvant Therapy; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011838:Radiation-Sensitizing Agents; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex