Journal
TRENDS IN CANCER
Volume 4, Issue 10, Pages 671-683Publisher
CELL PRESS
DOI: 10.1016/j.trecan.2018.08.003
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Funding
- CRUK
- Science Foundation Ireland (SFI)
- Health Research Board (HRB)
- Wellcome Trust under the SFI-HRB-Wellcome Trust Biomedical Research Partnership [103049/Z/13/Z]
- Breast Cancer Now
- Wellcome Trust [103049/Z/13/Z] Funding Source: Wellcome Trust
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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.
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