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Synthetic Lethality and Cancer - Penetrance as the Major Barrier.

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Publication Date
2018-10
ICR Author
Lord, Christopher
Author
Ryan, CJ
Bajrami, I
Lord, CJ
Type
Journal Article
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Abstract
Synthetic lethality has long been proposed as an approach for targeting genetic defects in tumours. Despite a decade of screening efforts, relatively few robust synthetic lethal targets have been identified. Improved genetic perturbation techniques, including CRISPR/Cas9 gene editing, have resulted in renewed enthusiasm for searching for synthetic lethal effects in cancer. An implicit assumption behind this enthusiasm is that the lack of reproducibly identified targets can be attributed to limitations of RNAi technologies. We argue here that a bigger hurdle is that most synthetic lethal interactions (SLIs) are not highly penetrant, in other words they are not robust to the extensive molecular heterogeneity seen in tumours. We outline strategies for identifying and prioritising SLIs that are most likely to be highly penetrant.
URL
https://repository.icr.ac.uk/handle/internal/2811
Collections
  • Breast Cancer Research
  • Molecular Pathology
Licenseref URL
http://www.rioxx.net/licenses/under-embargo-all-rights-reserved
Version of record
10.1016/j.trecan.2018.08.003
Subject
genetic screening
heterogeneity
penetrance
robustness
synthetic lethality
Research team
Gene Function
Language
eng
Date accepted
2018-08-22
License start date
2018-10
Citation
Trends Cancer, 2018, 4 (10), pp. 671 - 683

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