Emerging Importance of Survivin in Stem Cells and Cancer : the Development of New Cancer Therapeutics

• Survivin is one of the rare proteins that is differentially expressed in normal and cancer cells and is directly or indirectly involved in numerous pathways required for tumor maintenance. It is expressed in almost all cancers and its expression has been detected at early stages of cancer. These traits make survivin an exceptionally attractive target for cancer therapeutics. Even with these promising features to be an oncotherapeutic target, there has been limited success in the clinical trials targeting survivin. Only recently it has emerged that survivin was not being specifically targeted which could have resulted in the negative clinical outcome. Also, focus of research has now shifted from survivin expression in the overall heterogeneous tumor cell populations to survivin expression in cancer stem cells as these cells have proved to be the major drivers of tumors. Therefore, in this review we have analyzed the expression of survivin in normal and cancer cells with a particular focus on its expression in cancer stem cell compartment. We have discussed the major signaling pathways involved in regulation of survivin. We have explored the current development status of various types of interventions for inhibition of survivin. Furthermore, we have discussed the challenges involving the development of potent and specific survivin inhibitors for cancer therapeutics. Finally we have given insights for some of the promising future anticancer treatments.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Anticancer therapy

Cancer signaling

Cancer stem cells

Inhibitors

Survivin

1

4 diamino 1

4 bis(2 aminophenylthio) 2

3 dicyanobutadiene

2 (2 amino 3 methoxyphenyl)chromone

2 (2 chloro 4 iodoanilino) n cyclopropylmethoxy 3

4 difluorobenzamide

4 (3 bromoanilino) 6

7 dimethoxyquinazoline

4 (3 chloroanilino) 6

7 dimethoxyquinazoline

8 [4 (1 aminocyclobutyl)phenyl] 9 phenyl 1

2

4 triazolo[3

4 f][1

6]naphthyridin 3(2h) one

arctigenin

bay 11 7057

celecoxib

curcumin

etodolac

flavopiridol

gefitinib

idasanutlin

lapatinib

limonoid

mithramycin

monoclonal antibody

n tert butyl 3 [5 methyl 2 [4 (4 methyl 1 piperazinyl)phenylamino] 4 pyrimidinylamino]benzenesulfonamide

nanoparticle

nutlin 3

prodigiosin

resveratrol

salinomycin

sepantronium bromide

tolfenamic acid

trastuzumab

unclassified drug

unindexed drug

vasculotropin

antiapoptotic activity

cancer immunotherapy

cancer recurrence

cancer stem cell

cancer therapy

cell cycle phase

cell cycle progression

cell cycle regulation

cell differentiation

cell proliferation

cell reprogramming technique

chemoradiotherapy

chemosensitivity

DNA damage

DNA fragmentation

drug delivery system

embryonic stem cell

enzyme inhibition

flow cytometry

gene expression regulation

gene overexpression

gene repression

human

immune response

major histocompatibility complex

mitosis inhibition

molecularly targeted therapy

nonhuman

oncolytic virotherapy

priority journal

protein expression

protein function

protein structure

Review

ribozyme therapy

RNAi therapeutics

sequence analysis

signal transduction

stem cell self-renewal

transcription termination

upregulation

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