Table 2.

KRAS synthetic lethal genes

Library	Primary cell line screen – assay and format	Synthetic lethal genes	Refs
siRNA library targeting ~4,000 genes (protein kinases, G protein-coupled receptors, ubiquitin E3 ligases, transporters, ion channels and peptidases)	Isogenic KRAS G13D/WT human DLD-1 CRC cell lines – cell death (well-by-well)	BIRC5a, CDC2/ CDK1, C20ORF18/RBCK1	225
siRNA library targeting ~3,700 genes (protein kinases, G protein-coupled receptors, ubiquitin E3 ligases, transporters, ion channels, peptidases, phosphatases, dehydrogenases, nuclear receptors, lipid-modifying enzymes, integrins, chemokines and receptors)	Human NSCLC NCI-H1299 cell line (NRAS Q61K) – cell death (well-by-well)	RAN, TPX2, SCD1	226
Lentiviral shRNA library (5,024) targeting 1,011 genes (encoding kinases, phosphatases and cancer-related genes)	Panel of KRAS mutant (4) or WT (4) human AML, breast, CRC, glioblastoma and prostate tumour cell lines, and two nontransformed human lines – NHF and hTERT-HMEC – proliferation (well-by-well)	STK33, AKT3, CPNE1, CAMK1, MLKL, FLT3LG, DGKZ	227
Retroviral shRNA library (74,905) targeting 32,293 transcripts)	Isogenic KRAS G13D/WT DLD-1 CRC cell lines – proliferation (Pooled)	PLK1, APC/C, THOC1, Ubc9	143
Lentiviral shRNA library targeting 957 genes (including kinases, phosphatases and oncogenes)	Panel of KRAS mutant (7) and WT (10) human breast, CRC, glioblastoma, myeloma, NSCLC, prostate, renal tumour lines, and two nontransformed human cell lines - NHF, hTERT-HMEC – proliferation (well-by- well)	TBK1, PSKH2, PSMD14, PTCH2, CPNE1, MAPKP3K8	144
Lentiviral shRNA library (631) targeting 162 genes, including part of a Kras gene expression signature (n = 89), transcriptional regulators (n = 35) K-Ras effectors (n = 47), genes differentially expressed in human NSCLC samples (n = 20) or cell lines (n = 23)]	LKR10 and LKR13 Kras/Tp53 mutant mouse lung tumour-derived cell lines - proliferation in vitro and subcutaneous tumour growth in vivo in immunodeficient mice (pooled)	WT1	228
Retroviral shRNA library targeting 2,500 genes (protein kinases, cancer-related genes)	Isogenic KRAS G13D/WT HCT-116 CRC cell lines – proliferation (pooled)	SNAI2b	229
siRNA library targeting 7,000 genes of the druggable genome	Isogenic KRAS G13D/WT HCT-116 CRC cell lines – cell death (well-by-well)	CDC6, GATA2	145, 161
Lentivirus shRNA library targeting 17 protein kinases encoded by KRAS-dependent genes	KRAS-dependent (SW620) and -independent (SW837) human CRC cell lines (both KRAS mutant) – proliferation (well-by-well)	MAP3K7 c	230
Lentivirus shRNA library targeting 1,200 druggable genes, such as kinases and regulators of cell proliferation and survival	KRAS mutant CRC cell lines with different sensitivities to MEK/PI3K inhibition: HCT116 (sensitive) and SW620 (insensitive) – synergistic cell death with MEK inhibitor selumetinib treatment (pooled)	BCL2L1d	165
Lentiviral shRNA library targeting ~16,000 genes	72 RAS mutant or WT human breast, pancreatic, and ovarian tumour cell lines (pooled)	ARHGEF2e	152,231

AML, acute myelogenous leukaemia; CRC; colorectal carcinoma; HMEC, immortalized human mammary epithelial cells; NHF, normal human fibroblasts; NSCLC, non-small cell lung carcinoma;

^aEncodes Survivin;

^bEncodes Snail2;

^cEncodes TAK1;

^dEncodes Bcl-xL;

^eEncodes GEF-H1