Cancer cells rely on the expression of a limited number of specific genes for their survival, and these vulnerabilities are programmed by the underlying molecular features of tumors. Identifying these genetics-vulnerabilities relationships will yield a comprehensive catalog of the potential therapeutic targets for cancer and provide rationale for patient stratification. Several large-scale efforts are critical for this effort including the development of a collection of over 1000 cancer cell lines with comprehensive molecular characterization (Cancer Cell Line Encyclopedia) and the systematic use of RNA interference (RNAi) to identify Achilles' heels of cancers (Project Achilles). The Schreiber Lab in the Chemical Biology Program at the Broad Institute is taking a complementary approach utilizing well-annotated small molecules to identify cancer vulnerabilities (Broad Institute CTD2 Project). The construction of sophisticated computational models that predict vulnerabilities based on the molecular features of lung and other tumor types is the goal of our ICBP Project.