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BMC Cancer

, 14:203

Experimental therapeutics and drug development


BackgroundCompanion animals like dogs frequently develop tumors with age and similarly to human malignancies, display interpatient tumoral heterogeneity. Tumors are frequently characterized with regard to their mutation spectra, changes in gene expression or protein levels. Among others, these changes affect proteins involved in the DNA damage response DDR, which served as a basis for the development of numerous clinically relevant cancer therapies. Even though the effects of different DNA damaging agents, as well as DDR kinetics, have been well characterized in mammalian cells in vitro, very little is so far known about the kinetics of DDR in tumor and normal tissues in vivo.

DiscussionDue to i the similarities between human and canine genomes, ii the course of spontaneous tumor development, as well as iii common exposure to environmental agents, canine tumors are potentially an excellent model to study DDR in vivo. This is further supported by the fact that dogs show approximately the same rate of tumor development with age as humans. Though similarities between human and dog osteosarcoma, as well as mammary tumors have been well established, only few studies using canine tumor samples addressed the importance of affected DDR pathways in tumor progression, thus leaving many questions unanswered.

SummaryStudies in humans showed that misregulated DDR pathways play an important role during tumor development, as well as in treatment response. Since dogs are proposed to be a good tumor model in many aspects of cancer research, we herein critically investigate the current knowledge of canine DDR and discuss i its future potential for studies on the in vivo level, as well as ii its possible translation to veterinary and human medicine.

KeywordsCanine and human tumors DNA damage response DNA repair AbbreviationsATMAtaxia telangiectasia mutated

ATRATM and ataxia telangiectasia and Rad3-related protein

BERBase excision repair

BRCABreast cancer protein

BCR-ABLBreakpoint cluster region-Abelson murine leukemia viral oncogene homolog

53BP1p53-binding protein 1

CAECommon ancestor of eutherian

c-MetMNNG HOS transforming gene

CDKN2ACyclin-dependent kinase inhibitors 2A

CINChromosomal instability

CMLChronic myelogenous leukemia

CLLChronic lymphocytic leukemia-small lymphocytic lymphoma

CRCColorectal cancer

DDRDNA damage response

DNADeoxyribonucleic acid

DNA-PKcsDNA-dependent protein kinase, catalytic subunit

dsbDouble strand break

FISHFluorescence in situ hybridization

GHGrowth hormone

GHRGrowth hormone receptor

H2AXHistone variant 2AX

HER2Human epidermal growth factor receptor 2

HNSCCHead and neck squamous cell carcinoma

HRHomologous recombination

IGF-1Insulin-like growth factor 1

IRIonizing radiation

MDM2Mouse double minute 2 homolog

MnSODManganese superoxide dismutase


MSIMicrosatellite instability

MVCMinute virus of canines

Nbs1Nijmegen breakage syndrome 1

NERNucleotide excision repair

NHEJNon-homologous end joining

NHLNon-Hodgkin’s lymphoma

NIHNational institutes of health

PFGEPulse field gel-electrophoresis

RbRetinoblastoma protein

RPAReplication protein A

RTRadiation therapy

SCIDSevere combined immunodeficiency

SSBRSingle strand break repair

UV lightUltraviolet light.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-203 contains supplementary material, which is available to authorized users.

Barbara van Loon and Carla Rohrer Bley contributed equally to this work.

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Author: Nicole Grosse - Barbara van Loon - Carla Rohrer Bley

Source: https://link.springer.com/

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