Validating survivin as a cancer therapeutic target

Altieri, Dario C.

doi:10.1038/nrc968

Cited by 1,121 publications

(1,063 citation statements)

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“…In spite the fact that survivin act as inhibitor to effector caspases 3/7 and blocks the mutual downstream events of both apoptosis pathways [2], survivin awards tumor resistance to apoptosis and characterizes as an ideal molecular target for therapeutic interference. Most chemotherapeutic agents induce cell death in a mitochondria-dependent manner, yet death receptor-mediated signals can also be involved.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Esh

Atfy

Azizi

et al. 2011

Indian J Hematol Blood Transfus

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Impaired apoptosis is mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin. Survivin was described in number of different tumors and found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. The aim of this study was to determine survivin in pediatric ALL and compare it with clinical and hematological findings, response to therapy and outcome. Flowcytometry was used for detection of intracellular survivin and determine its mean fluorescence intensity (MFI) in bone marrow mononuclear cells. Patients were followed up for 28 months after induction therapy. Survivin was detected in 63.3% of the patients BM. In spite of no association of survivin levels with established risk factors (P [ 0.05) except with high WBC, there was significant higher level of survivin expression in high risk group patients when patients were stratified into high and standard risk groups. According to response to induction therapy, there was no significant difference, in survivin level between patients who achieved CR, RD and ED. However, patients suffering relapse of the disease, had a significant higher basal level of survivin than patients still in remission. Over expression of survivin is a candidate parameter to determine poor prognosis in ALL patients and it may serve to refine treatment stratification with intensification of therapy in those patients prone to relapse.

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Section: Discussionmentioning

confidence: 99%

“…Both apoptotic pathways for caspase activation converge on downstream effector caspases commonly result in activation of the effector caspases 3 and 7 [2].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Esh

Atfy

Azizi

et al. 2011

Indian J Hematol Blood Transfus

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“…The inhibition of survivin phosphorylation results in events that are associated with mitochondria-dependent apoptosis, such as cytochrome c release and caspase-9 activation. 4 Findings have suggested that survivin can physically associate with caspase-9 and that a loss of phosphorylation results in the dissociation of survivin from its complex with caspase-9 and subsequent caspase-9-dependent apoptosis. 42 However, there is still no direct evidence demonstrating that purified survivin can directly bind to and inhibit purified caspase-9.…”

Section: Discussionmentioning

confidence: 99%

“…3 Overexpression of survivin in different types of malignant tumor cells has been correlated with a poor prognosis. [4][5][6] Consequently, survivin overexpression is an important factor in tumor diagnosis and is a significant prognostic marker of cancer, including soft-tissue sarcoma. 7 Owing to its importance in tumorigenesis, survivin might be a suitable target for gene therapy approaches.…”

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confidence: 99%

Knockdown of survivin expression by small interfering RNA reduces the clonogenic survival of human sarcoma cell lines independently of p53

et al. 2004

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Survivin, a member of the inhibitors-of-apoptosis gene family, is overexpressed in many tumor types. Survivin is a prognostic marker of soft-tissue sarcomas, but the downregulation of survivin expression and the possible dependency of survivin downregulation on p53 in these tumors have not been investigated. Therefore, we applied small interfering RNA (siRNA) to knock down the expression of survivin in five human sarcoma cell lines with wild-type or mutant p53 alleles. Compared with survivin mRNA expression in the nonsense siRNA-treated sarcoma cell lines, expression after treatment with survivin-specific siRNA was reduced by 73-88%; survivin protein expression was reduced by 52-81%. This finding was coupled with a reduction in clonogenic survival ranging from 65-86%. However, less than 10% of cells treated with survivin-specific siRNA underwent apoptosis. Cell-cycle and morphologic analyses showed that after a dramatic increase in the number of treated cells in the G2/M phase, some of the cells became polyploid; this result indicates that mitosis of a substantial number of treated cells was incomplete. Our findings suggest that survivin-specific siRNA could be a selective treatment to kill sarcoma cells regardless of the presence or absence of wild-type p53 alleles.

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“…Recent studies have found several diagnostic biomarkers for loss of muscle mass such as N‐terminal peptide of procollagen type III, C‐terminal agrin fragment, leptin, ghrelin, and obestatin6, 7 and prognostic biomarkers in cancer patients such as matrix metalloproteinases, survivin, and butyrylcholinesterase 8, 9, 10. Although GDF15 might also be a useful prognostic marker in cancer patients, the small sample size, the heterogeneous population, and the selection bias could have some impacts on the findings in this study.…”

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confidence: 99%