TY - JOUR
T1 - Methodological approaches in application of synthetic lethality screening towards anticancer therapy
AU - Canaani, D.
N1 - Funding Information:
This work was supported by grants awarded to DC by the Public Health Service National Cancer Institute and the German Israeli Foundation (GIF). I am grateful to Dr Iris Dotan for critical reading of this manuscript. I thank the anonymous reviewers for their helpful comments. I apologise to my colleagues, whose work was not cited due to space and reference limitations.
PY - 2009/4/21
Y1 - 2009/4/21
N2 - A promising direction in the development of selective less toxic cancer drugs is the usage of synthetic lethality concept. The availability of large-scale synthetic low-molecular-weight chemical libraries has allowed HTS for compounds synergistic lethal with defined human cancer aberrations in activated oncogenes or tumour suppressor genes. The search for synthetic lethal chemicals in human/mouse tumour cells is greatly aided by a prior knowledge of relevant signalling and DNA repair pathways, allowing for educated guesses on the preferred potential therapeutic targets. The recent generation of human/rodents genome-wide siRNAs, and shRNA-expressing libraries, should further advance this more focused approach to cancer drug discovery.
AB - A promising direction in the development of selective less toxic cancer drugs is the usage of synthetic lethality concept. The availability of large-scale synthetic low-molecular-weight chemical libraries has allowed HTS for compounds synergistic lethal with defined human cancer aberrations in activated oncogenes or tumour suppressor genes. The search for synthetic lethal chemicals in human/mouse tumour cells is greatly aided by a prior knowledge of relevant signalling and DNA repair pathways, allowing for educated guesses on the preferred potential therapeutic targets. The recent generation of human/rodents genome-wide siRNAs, and shRNA-expressing libraries, should further advance this more focused approach to cancer drug discovery.
KW - Chemical genetic interactions
KW - Chemical synthetic lethality
KW - Genetic synthetic lethality
KW - Oncogenes
KW - RNAi
KW - Tumour suppressor genes
UR - http://www.scopus.com/inward/record.url?scp=64949199595&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605000
DO - 10.1038/sj.bjc.6605000
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C2 - 19319136
AN - SCOPUS:64949199595
SN - 0007-0920
VL - 100
SP - 1213
EP - 1218
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -
