김현석 (Hyun Seok Kim) 연세대학교 의과대학
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Cell, VOLUME 173, ISSUE 4, P864-878.E29. Published: April 19, 2018 | DOI: https://doi.org/10.1016/j.cell.2018.03.028
Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer
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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.



Category: Cell_Biology, Biochemistry, Molecular_Biology
등록일 2018.04.23
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