This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Reference
- Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer.
- Paper ID
- COSP45328
- Authors
- Affiliation
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Journal
-
Cell, 2018
ISSN: 1097-4172
PMID: 29681454 (view at PubMed or Europe PMC) - Abstract
- Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.
- Paper Status
- Curated
- Genes Analysed
- 47534
- Mutated Samples
- 126
- Total No. of Samples
- 126
