Targeting survivin in cancer therapy: fulfilled promises and open questions.
Survivin is a bifunctional protein that acts as a suppressor of apoptosis and plays a central role in cell division. The protein is strongly expressed in the most common human neoplasms, has prognostic relevance for some of them and appears to be involved in tumor cell resistance to 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 or function, accomplished by means of various strategies, reduced tumor growth potential, increased the apoptotic rate and sensitized tumor cells to chemotherapeutic drugs and radiation in different human tumor models. Moreover, the first survivin inhibitors recently entered clinical trials. Recent studies suggest a possible role for survivin in regulating the function of normal adult cells. However, the expression and function of survivin in normal tissues are still not well characterized and understood. Better knowledge of the role of survivin in tumor versus normal cells will be instrumental for the design of optimal strategies to selectively disrupt survivin in cancer.
Pennati
Marzia
M
Dipartimento di Oncologia Sperimentale, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, Italy.
Folini
Marco
M
Zaffaroni
Nadia
N
D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin