Drug-induced increase of carcinoembryonic antigen expression in cancer cells.
Most of gastrointestinal, breast and lung cancer cells express carcinoembryonic antigen (CEA). Therefore, this protein represents a suitable target for innovative diagnostic and immunotherapeutic strategies of various tumours. Presently CEA can be involved in three main approaches concerning cancer detection and therapy, i.e. (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides. Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine). Therefore, the use of drugs capable of increasing CEA expression, could amplify the sensitivity of diagnostic procedures that rely on CEA determination. Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC. The purpose of this review is to describe several agents that are able to increase CEA expression and to discuss the rational bases for new strategies in cancer detection and therapy aimed at increasing the expression of tumour-associated antigens.
Aquino
Angelo
A
Department of Neuroscience, University of Rome, Tor Vergata, 00133 Rome, Italy. angelo.aquino@uniroma@.it
Formica
Vincenzo
V
Prete
Salvatore Pasquale
SP
Correale
Pier Paolo
PP
Massara
Maria Chiara
MC
Turriziani
Mario
M
De Vecchis
Liana
L
Bonmassar
Enzo
E
D000818:Animals; D000970:Antineoplastic Agents / Q000145:classification / Q000494:pharmacology; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014415:Tunicamycin / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D000970:Antineoplastic Agents; D002087:Butyrates; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C015482:protein kinase modulator; D014415:Tunicamycin