Survivin as a target for new anticancer interventions.
Survivin is a member of the inhibitor of apoptosis protein (IAP) family, that has been implicated in both control of cell division and inhibition of apoptosis. Specifically, its anti-apoptotic function seems to be related to the ability to directly or indirectly inhibit caspases. Survivin is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. On the basis of these findings survivin has been proposed as an attractive target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression/function, accomplished through the use of antisense oligonucleotides, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors, increased the apoptotic rate, reduced tumor-growth potential and sensitized tumor cells to chemotherapeutic drugs with different action mechanisms and gamma-irradiation in in vitro and in vivo models of different human tumor types.
Zaffaroni
Nadia
N
Dipartimento di Oncologia Sperimentale, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. nadia.zaffaroni@istitutotumori.mi.it
Pennati
Marzia
M
Daidone
Maria Grazia
MG
D000970:Antineoplastic Agents / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference / Q000502:physiology; D016337:RNA, Catalytic / Q000627:therapeutic use; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D000077022:Survivin; C427204:hammerhead ribozyme; D018844:Cyclin-Dependent Kinases