The tumor therapy landscape of synthetic lethality

• DOI: 10.1038/s41467-021-21544-2
• Publication Date: 2021-02-24T11:03:35Z
• Authors: Biyu Zhang; Chen Tang; Yanli Yao; Xiaohan Chen; Chi Zhou; Zhiting Wei; Feiyang Xing; Lan Chen; Xiang Cai; Zhiyuan Zhang; Shuyang Sun; Qi Liu
• Keywords: Synthetic Lethality; Lethality

Abstract Synthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop Lethality Knowledge Graph (SLKG), presenting tumor therapy landscape of synthetic (SL) and dosage (SDL). SLKG integrates large-scale entity different tumors, drugs drug targets by exploring a set SL SDL pairs. The overall prioritized to identify best repurposable candidates combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, FDA-approved multiple sclerosis drug, selected identified treating melanoma CDKN2A mutation validation, serving demonstrating utility example novel discovery. Collectively, forms computational basis uncover cancer-specific susceptibilities strategies based on principle lethality.