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Mining Cellular Senescence for Drug Targets

  • Alan E. Bilsland
  • W. Nicol Keith
Chapter

Abstract

One of the fundamental changes required for tumorigenesis is escape from cellular senescence. Strategies to induce senescence in cancer cells might provide future therapies complementary to existing interventions aimed at apoptosis. Progress toward senescence targeted drug discovery could be accelerated by applying novel screening-technologies and in particular, cell-based screening approaches to identifing and validating small molecule agonists/effectors or stabilisers of senescence. In this chapter, we review the molecular bases of cellular senescence from a drug discovery perspective, highlighting existing therapies that induce senescence and strategies to expand the pool of candidate molecular targets.

Keywords

Telomere Length Malignant Pleural Mesothelioma Accelerate Senescence Senescent Cell Replicative Senescence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

53BP1

p53-Binding protein 1

Apaf-1

Apoptotic peptidase activating factor 1

ASF1a

Anti-silencing factor

ATM

Ataxia telangiectasia mutated

ATR

Ataxia telangiectasia and Rad3 related

Bad

BCL2-associated agonist of cell death

BAK

BCL2-antagonist/killer 1

BAX

BCL2-associated X protein

Bcl-2

B-cell CLL/lymphoma 2

Bid

BH3 interacting domain death agonist

CDK

Cyclin dependent kinase

CK1

Casein kinase 1

CRAMP

Cathelicidin-related antimicrobial protein

DAPI

4′,6-Diamidino-2-phenylindole

DC

Dyskeratosis congenita

DNA-PK

DNA dependent protein kinase

DNMT3a

DNA methyltransferase 3a

DRAM

Damage regulated autophagy modulator

EF-1a

Elongation factor 1a

ERK

Extracellular signal regulated kinase

FADD

Fas-associated via death domain

FasL

Fas ligand

FGF7

Fibroblast growth factor 7

GSK3

Glycogen synthase kinase 3

HIRA

HIR histone cell cycle regulation defective homolog A

HP1

Heterochromatin proteins 1

hTERT

Human telomerase reverse transcriptase

hTR

Human telomerase RNA component

IL-

Inteleukin-

JNK

c-Jun NH3 terminal kinase

LATS2

Large tumor suppressor, homolog 2

MeCP2

Methyl CpG binding protein 2

MEF

Mouse embryonic fibroblast

MSC

Mesenchymal stem cell

mTR

Mouse telomerase RNA component

NSCLC

Non small cell lung cancer

PCNA

Proliferating cell nuclear antigen

PI-3K

Phosphoinositide 3-kinase

PKC

Protein kinase C

POT1

Protection of telomeres 1

PUMA

p53-Upregulated modulator of apoptosis

RIP

Receptor interacting protein kinase

ROS

Reactive oxygen species

SAHF

Senescence-associated heterochromatin foci

SA-βGal

Senescence associated β-galactosidase

TIF

Telomere dysfunction induced damage foci

TIN2

TRF1 interacting nuclear factor 2

TNFα

Tumor necrosis factor α

TPP1

TIN2 interacting protein 1

TRADD

TNFRSF1-associated via death domain

TRAIL

TNF-related apoptosis inducing ligand

TRF1&2

telomeric repeat binding factors 1&2

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson LaboratoriesUniversity of GlasgowBearsden, GlasgowUK

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