Table 2 Identified key genes in synthetic lethality preclinical studies

ARID1A

1p36.11

Target SWI/SNF complexes, which regulate chromatin remodeling. SWI/SNF complexes are involved in controlling the cell cycle, DNA replication, and repairing DNA damage.

H1299, H2023, H2030

Smarca4-deficient genetically engineered mouse

Lung cancer

[34]

ATM

11q22.3

Activates cell cycle checkpoints; recognizes damaged DNA and triggers ATM-mediated DNA damage response pathway to repair damaged DNA strands.

KC (850, 6059, 8878), AKC (995, 5615, 5980, 5982)

AKC, KC, and SCID mouse

Pancreatic cancer

[35]

ATR

3q23

Cell cycle checkpoint signaling activation upon DNA stress and triggers ATR-mediated DNA damage sensing.

Human-derived CLL and Mec1 cell line

Primary CLL xenograft mouse

Leukemia

[36, 37]

BRCA1

17q21.31

Repair DNA double-strand breaks via ubiquitination, transcriptional regulation, and homologous recombination.

A2780, HEK293, SUM149PT

N/A

Ovarian cancer

[38]

BRCA2

13q13.1

Repair DNA double-strand breaks via ubiquitination, transcriptional regulation, and homologous recombination.

PL2F7, Y3308Y

BRCA-deficient mouse

N/A

[39]

CDC6

17q21.2

Initiation of DNA replication; regulates cell cycle.

HCT-116, HKE-3

KRAS-induced lung cancer mouse

Lung cancer

[40, 41]

CDK1

10q21.2

Regulate cell cycle (G1/S and G2/M phase transitions).

LIM1215, SW48

KRAS-mutated mouse

N/A

[42]

CDK2

12q13.2

Regulate cell cycle (G1/S phase transition).

HACAT

N/A

N/A

[43, 44]

CDK17

12q23.1

Serine-threonine protein kinase; regulate G2/M phase transition.

HeLa, K562, MCF10A, MDA-MB-231, RPE1

N/A

Breast cancer

[45]

CHEK1

11q24.2

Serine-threonine protein kinase; triggers cell cycle arrest in response to DNA damage; integrate signals from ATR and ATM; phosphorylation of CDC25A to delay cell cycle progression following DNA double-strand breaks.

PEO14, PEO23, SKOV3

SKOV3 xenograft mouse

Ovarian cancer

[46]

CHEK2

22q12.1

Serine-threonine protein kinase; triggers cell cycle arrest in response to DNA damage; integrate signals from ATR and ATM; phosphorylation of CDC25A to delay cell cycle progression following DNA double-strand breaks.

Cal27, HN30, HN31, SCC61, UMSCC17A

N/A

Head and neck cancer

[47]

GATA2

3q21.3

Zinc-finger transcription factor; regulate transcription genes.

A549, H226, HL7702

A549 xenograft mouse

Lung cancer

[48]

KRAS

12p12.1

Transcriptional activator that regulates endothelial cells endothelin-1 gene expression.

A549, H441

A549 xenograft mouse

Lung cancer

[49, 50]

MRE11

11q21

MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint.

V-C8

N/A

N/A

[51]

MYC

8q24.21

Regulate cell cycle progression, transcription, and apoptosis.

Kelly, BE-2C, NLF, SK-N-AS, SHEP, MYCN-ER

BALB/c nude mouse

Neuroblastoma

[52, 53]

NBN

8q21.3

MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint.

B220, Gr-1, Mac-1

Nbn-mutated mouse

Leukemia

[54]

PAK3

Xq23

Serine-threonine protein kinase; regulates cell cycle, cell migration, and apoptosis.

CaSki, HeLa, HFK, SiHa

N/A

Cervical cancer

[55]

PARP1

1q41.42

Regulate cell proliferation and differentiation; repair DNA single- and double-strand breaks.

DLD-1, HEK293FT, KB1P-G3, KB2P, SUM149PT, U2OS

BRCA2-mutated mouse

Breast and ovarian cancer

[56]

PLK1

16p12.2

Serine-threonine protein kinase; regulate cell proliferation and apoptosis; triggers G2/M transition.

A549, H441, H522, T29

BALB/c and C57BL/6 nude mouse

Lung cancer

[57]

RAD50

5q31.1

MRN complex component; DNA double-strand breaks repair via nonhomologous end-joining and homologous recombination activation in ATM-mediated checkpoint.

D1241, L1240, Q1262, WT

N/A

Metastatic small cell cancer

[58]

RAD51

15q15.1

Repair DNA double-strand breaks via homologous recombination.

HeLa, K562, M059, U2OS

N/A

N/A

[59]

TP53

17p13.1

Major tumor suppressor; regulate cell cycle, senescence, and apoptosis.

C4-2, LNCaP, U2OS

NSG mouse

Prostate cancer

[60, 61]

53BP1

15q15.3

Repair DNA double-strand breaks by promoting non-homologous end-joining pathways while limiting homologous recombination.

DOHH2, G452, HCC1187 OCI-LY (1, 8, 19), SUDHL-6, U2932, VAL

NOD, NSG, and SCID mouse

Lymphoma

[62, 63]

WEE1

11p15.4

Serine-threonine protein kinase; regulates G2/M checkpoint via CDC2 inhibition.

MCF7, MDA-MB-231, T-47D, Zr-75-1

Breast cancer xenograft NSG mouse

Breast cancer

[64]