Table 1.
Whole-genome or targeted screens for genetic determinants for PARP inhibitor response
| Screen context | Drug response | Cell line used and genetic status | PAR status | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Reference | DOI | Year of publication | BRCA1-/- | BRCA2-/- | Targets | Library | PARPi | Other drug | PARPi response upon gene loss | Cell line | Genetic status | Cell type | Non covalent PAR binding | Covalent PARylation |
| He et al. | doi:10.1038/s41586-018-0670-5 | 2018 | ✓ | X | DYNLL1 | Updated GeCKO library | Olaparib | Cisplatin | Resistant | UWB1.289 | BRCA1-mut | Ovarian cancer | ✓ | |
| COV362 | BRCA1-mut | Ovarian cancer | ||||||||||||
| JHOS-2 | BRCA1-mut | Ovarian cancer | ||||||||||||
| Pettitt et al. | doi: 10.1038/s41467-018-03917-2 | 2018 | ✓ | X | PARP1mut | Tzelepis et al., 2016 | Talazoparib | ✓ | Resistant | SUM149PT | BRCA1-mut | Breast cancer | ✓ | ✓ |
| Mouse ES cells | - | Embryonic Stem cells | ||||||||||||
| Barazas et al. | https://doi.org/10.1016/j.celrep.2018.04.046 | 2018 | ✓ | X | CTC1 | Costantino et al., 2014; Xu et al., 2015 | Olaparib/ Talazoparib/ AZD2461 | ✓ | Resistant | KBB1P.G3 | BRCA1-mut | Breast cancer | ||
| Mouse ES cells | BRCA1-mut | Embryonic Stem cells | ||||||||||||
| SUM149PT | BRCA1-mut | Breast cancer | ||||||||||||
| Noordermeer et al. | doi:10.1038/s41586-018-0340-7 | 2018 | ✓ | X | SHLD complex | TKOv1 sgRNA library | Olaparib/ Talazoparib | ✓ | Resistant | RPE1-hTERT TP53-/- | BRCA1-/- | Retinoblastoma | ||
| SUM149PT | BRCA1-mut | Breast cancer | ||||||||||||
| Dev et al. | doi:10.1038/s41556-018-0140-1 | 2018 | ✓ | X | c20orf196 (SHLD1) | GeCKOv2 | Olaparib/ Talazoparib/ ADZ2461 | ✓ | Resistant | SUM149PT | BRCA1-mut | Breast cancer | ||
| FAM35A (SHLD2) | Resistant | |||||||||||||
| Marzio et al. | doi:10.1016/j.molcel.2018.11.003 | 2019 | ✓ | X | EMI1 | 69 siRNA SMARTpool library againt human F-BOX69 siRNA SMARTpool library againt human F-BOX69 siRNA SMARTpool library againt human F-BOX | Olaparib | ✓ | Resistant | SUM149PT | BRCA1-mut | Breast cancer | ✓ | |
| Shinoda et al. | doi:10.1016/j.molcel.2021.03.034 | 2021 | X | ✓ | THAP | Genome-scale mouse Brie CRISPR knockout pooled library | Olaparib | ✓ | Resistant | MEF | BRCA1-mut +/-p53 | Mouse embryonic fibroblasts | ||
| Paes Dias et al. | https://doi.org/10.1016/j.molcel.2021.09.005 | 2021 | X | ✓ | LIG3 | pLKO.1; DDR library derived from the Sigma Mission library (TRCMm1.0) (lentiviral hairpins) | Olaparib | ✓ | Sensitive | 2D and 3D (KB1P4.R1) mESC | TP53-/- TP53BP1-/- | Mice Embryonic Stem Cells | ✓ | ✓ |
| Gogola et al. | doi:10.1016/j.ccell.2018.05.008 | 2018 | X | ✓ | PARG | 1976 shRNA custom library | Olaparib/ AZD2461 | ✓ | Resistant | KB2P1.21 | BRCA2-/- | Breast cancer | ✓ | ✓ |
| KB2P3.4 | BRCA2-/- | Breast cancer | ||||||||||||
| ORG-KB2P26S.1 | BRCA2-/- | Breast cancer | ||||||||||||
| Mengwasser et al. | doi:10.1016/j.molcel.2018.12.008. | 2019 | X | ✓ | FEN1 | Custom shRNA library | ✓ | ✓ | Sensitive | DLD-1 | BRCA2-mut | Colon adenocarcinoma | ✓ | ✓ |
| APEX2 | Sensitive | ✓ | ||||||||||||
| Clements et al. | doi:10.1038/s41467-020-19961-w | 2020 | X | ✓ | HUWE1 | Brunello Human CRISPR knockout pooled library | Olaparib | ✓ | Resistant | HeLa | BRCA2-/- | Cervix adenocarcinoma | ✓ | ✓ |
| KAT5 | Resistant | |||||||||||||
| Kharat et al. | doi:10.1126/scisignal.aba8091 | 2020 | ✓ | ✓ | TET2 | Ambion Silencer Mouse Genome siRNA collection | Olaparib | - | Resistant | mESC | Hypomorphic BRCA2 | Mice Embryonic Stem Cells | ||
| Tang et al. | doi:10.1093/nar/gkab540 | 2021 | ✓ | ✓ | Cyclin C | TKOv3 gRNA library | Olaparib | ✓ | Resistant | HEK293A | BRCA2-/- | Human Embryonic Kidney cells | ||
| Turner et al. | doi:10.1038/emboj.2008.61 | 2008 | ✓ | ✓ | CDK5 | siARRAY, targeting 779 known and putative human protein kinase genes | KU0058948 | ✓ | Sensitive | CAL51 | BRCA2-mut +/- siBRCA1 | Breast cancer | ✓ | |
| Bajrami et al. | doi:10.1158/0008-5472.CAN-13-2541 | 2014 | ✓ | ✓ | CDK12 | OpenBiosystems GIPZ human shRNA library | Olaparib | ✓ | Sensitive | MCF-7 | - | Breast cancer | ✓ | |
| Verma et al. | doi:10.1038/s41556-020-00624-3. | 2021 | ✓ | ✓ | ALC1 | Domain-focused sgRNA pooled library (custom) | Olaparib/ Talazoparib | ✓ | Sensitive | CAPAN-1 | BRCA2-mut | Pancreatic adenocarcinoma | ✓ | ✓ |
| SUM149PT | BRCA1-mut | Breast cancer | ||||||||||||
| UWB1.289 | BRCA1-mut | Ovarian cancer | ||||||||||||
| Zimmermann et al. | doi:10.1038/s41586-018-0291-z | 2018 | - | - | RNAseH2 | TKOv1 virus library | Olaparib | ✓ | Sensitive | HeLa | - | Cervix adenocarcinoma | ✓ | ✓ |
| RPE1-hTERT | - | Retinoblastoma | ||||||||||||
| SUM149PT | BRCA1-mut | Breast cancer | ||||||||||||
| Fang et al. | doi:10.1038/s42003-019-0580-6 | 2019 | - | - | TIGAR | GeCKO v2.0 pooled libraries | Olaparib | ✓ | Sensitive | A2780 | - | Ovarian cancer | ||
| Lui et al. | doi:10.1016/j.ebiom.2020.102988 | 2020 | - | - | BRD4 | Custom siRNA library | Rucaparib | ✓ | Sensitive | Patient's derived OCI-C5x and OCI-P5x cells | Some BRCA1-mut | Ovarian cancer | ✓ | |
| Juhasz et al. | doi:10.1126/sciadv.abb8626 | 2020 | - | - | ALC1 | GeCKOv2 | Olaparib | ✓ | Sensitive | HeLa | - | Cervix adenocarcinoma | ✓ | ✓ |
| Su et al. | doi:10.1016/j.dnarep.2020.102803 | 2020 | - | - | POLE3/4 | DDR-focused CRISPR library targeting 365 genes (custom) | Olaparib | KU55933, AZD6738, LY2606368, hydroxyurea, cisplatin, MMC, camptothecin and etoposide | Sensitive | HEK293A | TP53-/- | Human Embryonic Kidney cells | ||
| Hewitt et al. | doi:10.1016/j.molcel.2020.12.006 | 2021 | - | - | BRCA2 | Brunello Human CRISPR knockout pooled library | Olaparib | ✓ | Sensitive | eHAP | ALC1-/- | Chronic myelogenous leukemia cells | ✓ | |
| ATM | Sensitive | ✓ | ✓ | |||||||||||
| UBC13 | Sensitive | ✓ | ✓ | |||||||||||
| SMUG1 | Resistant | |||||||||||||
| Fugger et al. | doi:10.1126/science.abb4542 | 2021 | - | - | DNPH1 | Brunello Human CRISPR knockout pooled library | Olaparib | ✓ | Sensitive | eHAP | MUS81 -/- | Chronic myelogenous leukemia cells | ||
| Ipsen et al. | doi:10.1038/s41388-022-02427-2 | 2022 | - | - | PARP-1 | Brunello Human CRISPR knockout pooled library | Olaparib | ✓ | Resistant | C4 | - | Castration-resistant prostate cancer | ✓ | ✓ |
| ARH3 | Resistant | ✓ | ||||||||||||
| YWHAE | Resistant | ✓ | ✓ | |||||||||||
| UBR5 | Resistant | |||||||||||||
| Zhang et al. | doi:10.3389/fonc.2022.999302 | 2022 | - | - | TBL1XR1 | Cellecta KOHGW-80K-P library | Olaparib | ✓ | Sensitive | 22Rv1 | - | Prostate carcinoma | ✓ | |
| Xu et al. | doi: 10.1158/1541-7786.MCR-20-0791 | 2022 | - | - | CHK2 | Custom pooled DNA repair lentiviral sgRNA library | Olaparib | - | Resistant | Eμ-Myc mouse lymphoma | - | B-cell lymphoma | ||
| Zimmermann et al. | https://doi.org/10.1016/j.celrep.2022.111081 | 2022 | - | - | RNASEH2B | TKOv3 sgRNA library | Niraparib | RP-3500 (ATRi) | Sensitive | RPE1-hTERT TP53-/- | TP53-/- | Human Embryonic Kidney Cells | ✓ | |
| RAD51B | Sensitive | |||||||||||||
| RAD51C | Sensitive | |||||||||||||
| RAD51D | Sensitive | |||||||||||||
| Tsujino et al. | doi:10.1038/s41467-023-35880-y | 2023 | - | - | MMS22L | CRISPR-Cas9 KO H1 and H2 libraries obtained from Drs. Myles Brown and X. Shirley Liu's laboratories | Olaparib | ✓ | Resistant | LNCaP, C4-2B, 22Rv1 and DU145 cells | DU145: BRCA2d12 | Prostate carcinoma | ||
| CHK2 | Resistant | |||||||||||||
| E2F7 | Resistant | ✓ | ||||||||||||