Synthetic Lethality and Cancer - Penetrance as the Major Barrier.
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Embargo End Date
ICR Authors
Authors
Ryan, CJ
Bajrami, I
Lord, CJ
Bajrami, I
Lord, CJ
Document Type
Journal Article
Date
2018-10-01
Date Accepted
2018-08-22
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.
Citation
Trends in cancer, 2018, 4 (10), pp. 671 - 683
Source Title
Publisher
CELL PRESS
ISSN
2405-8033
eISSN
2405-8025
Collections
Research Team
Gene Function