The tumor therapy landscape of synthetic lethality

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 the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Nature communications - 12(2021), 1 vom: 24. Feb., Seite 1275

Sprache:

Englisch

Beteiligte Personen:

Zhang, Biyu [VerfasserIn]
Tang, Chen [VerfasserIn]
Yao, Yanli [VerfasserIn]
Chen, Xiaohan [VerfasserIn]
Zhou, Chi [VerfasserIn]
Wei, Zhiting [VerfasserIn]
Xing, Feiyang [VerfasserIn]
Chen, Lan [VerfasserIn]
Cai, Xiang [VerfasserIn]
Zhang, Zhiyuan [VerfasserIn]
Sun, Shuyang [VerfasserIn]
Liu, Qi [VerfasserIn]

Links:

Volltext

Themen:

47M74X9YT5
CDKN2A protein, human
Cladribine
Cyclin-Dependent Kinase Inhibitor p16
Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 03.03.2021

Date Revised 12.03.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-021-21544-2

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321859464