Synthetic Lethality and Cancer - Penetrance as the Major Barrier.
Date
2018-10-01ICR Author
Author
Ryan, CJ
Bajrami, I
Lord, CJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Neoplasms
Computational Biology
RNA Interference
Penetrance
Oncogenes
Molecular Targeted Therapy
Genetic Therapy
CRISPR-Cas Systems
Gene Editing
Synthetic Lethal Mutations
Research team
Gene Function
Language
eng
Date accepted
2018-08-22
License start date
2018-10
Citation
Trends in cancer, 2018, 4 (10), pp. 671 - 683
Publisher
CELL PRESS