Synthetic lethality as an engine for cancer drug target discovery

A Huang, LA Garraway, A Ashworth… - Nature reviews Drug …, 2020 - nature.com
The first wave of genetically targeted therapies for cancer focused on drugging gene
products that are recurrently mutated in specific cancer types. However, mutational analysis …

Synthetic lethality in cancer therapeutics: the next generation

J Setton, M Zinda, N Riaz, D Durocher, M Zimmermann… - Cancer discovery, 2021 - AACR
Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not
classically “druggable,” including loss-of-function mutations in tumor suppressor genes …

Synthetic lethality and cancer–penetrance as the major barrier

CJ Ryan, I Bajrami, CJ Lord - Trends in cancer, 2018 - cell.com
Synthetic lethality has long been proposed as an approach for targeting genetic defects in
tumours. Despite a decade of screening efforts, relatively few robust synthetic lethal targets …

[HTML][HTML] CRISPR-Cas9 library screening approach for anti-cancer drug discovery: overview and perspectives

YT Chan, Y Lu, J Wu, C Zhang, HY Tan, Z Bian… - Theranostics, 2022 - ncbi.nlm.nih.gov
CRISPR-Cas9 is a Nobel Prize-winning robust gene-editing tool developed in the last
decade. This technique enables a stable genetic engineering method with high precision on …

CRISPR/Cas9 library screening for drug target discovery

M Kurata, K Yamamoto, BS Moriarity… - Journal of Human …, 2018 - nature.com
CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-
based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries …

Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials

A Lin, CJ Giuliano, A Palladino, KM John… - Science translational …, 2019 - science.org
Ninety-seven percent of drug-indication pairs that are tested in clinical trials in oncology
never advance to receive US Food and Drug Administration approval. While lack of efficacy …

Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes

JE Neggers, B Kwanten, T Dierckx, H Noguchi… - Nature …, 2018 - nature.com
Unraveling the mechanism of action and molecular target of small molecules remains a
major challenge in drug discovery. While many cancer drugs target genetic vulnerabilities …

SynLethDB 2.0: a web-based knowledge graph database on synthetic lethality for novel anticancer drug discovery

J Wang, M Wu, X Huang, L Wang, S Zhang, H Liu… - Database, 2022 - academic.oup.com
Two genes are synthetic lethal if mutations in both genes result in impaired cell viability,
while mutation of either gene does not affect the cell survival. The potential usage of …

Development of synthetic lethality in cancer: molecular and cellular classification

S Li, W Topatana, S Juengpanich, J Cao, J Hu… - … and Targeted Therapy, 2020 - nature.com
Recently, genetically targeted cancer therapies have been a topic of great interest. Synthetic
lethality provides a new approach for the treatment of mutated genes that were previously …

CRISPR–Cas: a tool for cancer research and therapeutics

H Yin, W Xue, DG Anderson - Nature reviews Clinical oncology, 2019 - nature.com
In the past decade, the development of a genome-editing technology mediated by CRISPR
has made genetic engineering easier than ever, both in vitro and in vivo. CRISPR systems …