Table 5 Anticancer drugs and the hypertolerant phenotype of yeast strains heterozygous for the HP gene encoding their target protein
| Drug | Concentration in solid medium (uM) | Concentration in liquid medium (uM) | Mode of action | Specific HP genetic target (yeast/human) | Hyper-tolerant yeast strains |
Cancer in which CNV-reduction of the gene deleted in the hypertolerant strain occurs |
|---|---|---|---|---|---|---|
| RAD54/RAD54L | ||||||
| Cycloheximide | 0.36, 1.8 | 0.1 | Inhibition of translation | RIM11/GSK3B | IRR1/irr1 | - |
| Mitoxantrone | 10, 25 | - | TOPII inhibition | TOP2/TOP2A | - | - |
| NBP2/nbp2 | ||||||
| GPD1/gpd1 | Serous adenocarcinoma (NBP2) | |||||
| Methotrexate | 200 | 2, 100 | Inhibition of nucleoside and purine synthesis | MET7/FPGS | RIM11/rim11 | Renal cell carcinoma (GPD1) |
| Phleomycin | 1, 2 | 0.1, 0.5 | DNA strand break induction | - | MET7/met7 | Serous adenocarcinoma |
| 5-fluorouracil | 200 | 2, 100 | Inhibition of pyrimidine synthesis | - | IDP1/idp1 | - |
| Tamoxifen | 25 | - | Estrogen receptor antagonist | - | - | - |
| NBP2/nbp2 | ||||||
| Aminopterin | 10 | 0.1,1, 5, 10, 50, 100 | Inhibition of DNA, RNA & protein synthesis | - | TOP1/top1 | Serous adenocarcinoma |
| SAHA/vorinostat | 10, 20 | - | Histone deacetylase inhibition | RPD3/HDAC2 | - | - |
| Bay 11-7085 | 20, 40 | - | NF-kB TF inhibitior; proapoptotic agent | - | - | - |
| Cantharidin | 30, 60 | 6, 30 | Inhibition of PP2A | TPD3 | UBX4/ubx4 | - |
| PD98059 (2'-amino-3'-methylflavone) | 40, 80 | 4 | MEK1 MAPK inhibition | PBS2/MAP2K1 | NBP2/nbp2 | Serous adenocarcinoma |
| HRK1/hrk1 | ||||||
| MLH1/mlh1 | ||||||
| Hydroxyurea | 100000, 200000 | 100, 1000 | Inhibition of DNA synthesis; DSB induction | RAD54/RAD54L | STP22/stp22 | Renal cell carcinoma (MLH1) |
| Lithium chloride | - | Alternative RIM11 inhibitor | RIM11/GSK3B | - | ||
| Caffeine | 1000, 5000 | - | Alternative RAD54 inhibitor | RAD54/RAD54L | - | |
| Methyl methanesulfonate | - | DNA methylation, causing DSB or stalled replication forks | - | - | ||
| DPI | 10, 20 | - | NAD(P)H oxidase inhibition | - | - | |
| Tert-butyl hydroperoxide (TBHP) | - | Free-radical generation | - | - | ||
| Clotrimazole | 2.5, 5, 7.5 | - | Antifungal; increases cell wall permeability | - | - |