Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer

Publication date: Available online 19 April 2018 Source:Cell Author(s): Elizabeth A. McMillan, Myung-Jeom Ryu, Caroline H. Diep, Saurabh Mendiratta, Jean R. Clemenceau, Rachel M. Vaden, Ju-Hwa Kim, Takashi Motoyaji, Kyle R. Covington, Michael Peyton, Kenneth Huffman, Xiaofeng Wu, Luc Girard, Yeojin Sung, Pei-Hsaun Chen, Prema L. Mallipeddi, Joo Young Lee, Jordan Hanson, Sukesh Voruganti, Yunku Yu, Sunho Park, Jessica Sudderth, Christopher DeSevo, Donna M. Muzny, HarshaVardhan Doddapaneni, Adi Gazdar, Richard A. Gibbs, Tae-Hyun Hwang, John V. Heymach, Ignacio Wistuba, Kevin R. Coombes, Noelle S. Williams, David A. Wheeler, John B. MacMillan, Ralph J. Deberardinis, Michael G. Roth, Bruce A. Posner, John D. Minna, Hyun Seok Kim, Michael A. White 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...

Source: Cell - April 20, 2018 Category: Cytology Source Type: research