Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions.
Survivin is a structurally unique member of the inhibitors of apoptosis protein (IAP) family that is involved in both control of cell division and inhibition of apoptosis. Its anti-apoptotic function seems to be related to its ability to directly or indirectly inhibit caspases, although the precise role of survivin in the modulation of the caspase cascade has not been fully elucidated. Survivin has been described to be selectively expressed in the most common human neoplasms and to be associated with clinical tumour progression. Moreover, the protein appears to be involved in tumour cell resistance to some anticancer agents and ionizing radiation. On the basis of these findings survivin has been proposed as a promising target for new anticancer interventions. In in vitro and in vivo studies targeting survivin with antisense oligonucleotides, dominant negative mutants or ribozymes have shown to induce apoptosis, reduce tumour-growth potential and sensitise tumour cells to chemotherapeutic drugs such as Taxol, cisplatin and etoposide, gamma-irradiation, and immunotherapy.
Dipartimento di Oncologia Sperimentale, Istituto Nazionale per lo Studio e la Cura dei Tumori, Unita' Operativa 10, Via Venezian 1, 20133 Milan, Italy. zaffaroni@institutotumori.mi.it
Nadia
N
Zaffaroni
Maria Grazia
MG
Daidone
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin