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Targeting Survivin in Cancer Therapy: Pre-clinical Studies

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Apoptosome

Abstract

Survivin is a structurally unique member of the inhibitor of apoptosis protein family that in addition to acting as a suppressor of programmed cell death also plays a central role in cell division. Owing to its massive up-regulation in human tumors and its involvement in cancer progression and treatment resistance, survivin is currently undergoing extensive investigation as a promising target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression or function, accomplished by means of various strategies (including the use of antisense oligonucleotides, small interfering RNAs, ribozymes, dominant negative mutants and small molecule antagonists), reduced tumor growth potential, increased the apoptotic rate, and sensitized tumor cells to chemotherapeutic drugs and ionizing radiation in different human tumor preclinical models. Moreover, the first survivin inhibitors have already reached the clinic with some promise. However, due to its documented role in some normal tissues, the possibility that survivin disruption could affect normal cell function, mainly the hematopoietic and immune systems, cannot be excluded. In this context, a better understanding of the effects exerted by survivin on normal versus malignant cells will be important for the design of optimal strategies to selectively disrupt survivin in cancer.

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Abbreviations

BIR:

Baculovirus IAP repeat

CDK:

Cyclin-dependent kinase

Hsp90:

Heat shock protein 90

ILP2:

IAP-like protein 2

IAP:

Inhibitor of apoptosis protein

INCENP:

Inner centromere protein

ML-IAP:

Melanoma inhibitor of apoptosis

NAIP:

Neuronal apoptosis inhibitor protein

NSCLC:

Non-small cell lung cancer

PSA:

Prostate-specific antigen

Smac/Diablo:

Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI

siRNA:

Small interfering RNA

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

X-IAP:

X-linked inhibitor of apoptosis.

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Authors and Affiliations

  1. Dipartimento di Oncologia Sperimentale, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Marzia Pennati, Marco Folini & Nadia Zaffaroni

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  1. Marzia Pennati
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  2. Marco Folini
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  3. Nadia Zaffaroni
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Correspondence to Nadia Zaffaroni .

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  1. Dipto. Biologia, Università di Roma, Tor Vergata, Via della Ricerca Scientifica, Roma, 00133, Italy

    Francesco Cecconi

  2. IRCCS, Fondazione Santa Lucia, Via Fosso di Fiorano, Roma, 00143, Italy

    Marcello D'Amelio

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Pennati, M., Folini, M., Zaffaroni, N. (2010). Targeting Survivin in Cancer Therapy: Pre-clinical Studies. In: Cecconi, F., D'Amelio, M. (eds) Apoptosome. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3415-1_8

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