Discovering and Validating Cancer Genetic Dependencies: Approaches and Pitfalls

Lin, A., Sheltzer, J.M. (June 2020) Discovering and Validating Cancer Genetic Dependencies: Approaches and Pitfalls. Nat Rev Genet. ISSN 1471-0056

DOI: 10.1038/s41576-020-0247-7


Cancer 'genetic dependencies' - genes whose products are essential for cancer cell fitness - are promising targets for therapeutic development. However, recent evidence has cast doubt on the validity of several putative dependencies that are currently being targeted in cancer clinical trials, underscoring the challenges inherent in correctly identifying cancer-essential genes. Here we review several common techniques and platforms for discovering and characterizing cancer dependencies. We discuss the strengths and drawbacks of different gene-perturbation approaches, and we highlight the use of poorly validated genetic and pharmacological agents as a common cause of target misidentification. A careful consideration of the limitations of current technologies and cancer models will improve our ability to correctly uncover cancer genetic dependencies and will facilitate the development of improved therapeutic agents.

Item Type: Paper
CSHL Authors:
Communities: CSHL labs > Sheltzer lab
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
Depositing User: Adrian Gomez
Date: 19 June 2020
Date Deposited: 23 Jun 2020 12:15
Last Modified: 05 Nov 2020 20:52
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