Table 2 Studies on Synthetic Lethal Screen in CDH1-deficient Cancers
No. | Cancer Type | Study Model | Target(s) | Drug(s) | Main Findings | Reference |
|---|---|---|---|---|---|---|
1. | Breast and gastric carcinoma | Breast and gastric cancer cell lines with CDH1 knockout | ROS 1 | Crizotinib and Foretinib | Induced mitotic abnormalities and multi-nucleation in E-cadherin deficient cells | [68] |
2. | Mammary epithelial cell line | MCF10A and isogenic line with CDH1 knockout | Histone deacetylase, PI3K and tyrosine kinase | Vorinostat, Entinostat | Linkages to GPCR signalling and cytoskeletal function that showed evidence of E-cadherin synthetic lethality | [70] |
PI3K | PI103 | |||||
Tyrosine kinase | Crizotinib, Saracatinib | |||||
3. | – | 12 novel lead-like compounds | Preferentially harmed E-cadherin-deficient cells | [71] | ||
4. | Multiple kinases (eg. BCR-ABL, DDR2, Src) | Dasatinib | Preferentially slowed growth and induced apoptosis of E-cadherin-deficient cells | [69] | ||
5. | Mammary epithelial cell line and gastric adenocarcinoma | MCF10A and NCI-N87 isogenic lines with CDH1 knockout | PI3K/ AKT | PI103 | CDH1-null cells more sensitive than wild-type cells to compounds that disrupted plasma membrane composition and trafficking | [72] |
G-protein coupled receptor | Bafilomycin A1 | |||||
Ion channels | NS3728 | |||||
Proteosomal subunit proteins | Latrunculin B, Cytochalasin D | |||||
Ubiquitinylation enzymes | Ethyl-β-cyclodextrin | |||||
6. | AKT | ARQ-092, MK2206 | CDH1 null cells were more sensitive to allosteric AKT inhibitors | [73] |