TABLE 1.
DDR inhibitors
| DDR pathway | Genes | DDR inhibitors | Application | Ref |
|---|---|---|---|---|
| BER | PARP | Olaparib (AD2281) | Germline BRCA‐mutated metastatic pancreatic cancer (NCT02184195) | (97) |
| Combination with irinotecan, cisplatin, and mitomycin C in pancreatic cancer (NCT01296763) | (98) | |||
| Combination with gemcitabine in pancreatic cancer (NCT00515866) | ||||
| Metastatic pancreatic cancer with a BRCAness somatic profile (NCT04348045) | ||||
| Veliparib (ABT‐888) | Combination with gemcitabine, cisplatin pancreatic cancer with BRCA1/2, PALB2 mutation (NCT01585805) | |||
| Combination with folinic acid, fluorouracil and irinotecan (FOLFIRI) in pancreatic cancer (NCT02890355) | ||||
| Combination with modified FOLFOX6 in pancreatic cancer (NCT01489865) | ||||
| Combination with gemcitabine and intensity modulated radiation therapy in pancreatic cancer (NCT01908478) | ||||
| Niraparib (MK‐4827) | Pancreatic cancer with BRCA1, BRCA2, PALB2, CHEK2 or ATM mutations (NCT03601923) | |||
| Pancreatic cancer after previous chemotherapy (NCT03553004) | ||||
| Talazoparib (BMN 673) | Advanced or recurrent solid tumors, including pancreatic cancer with BRCA mutations (NCT01286987) | (99) | ||
| Rucaparib (AG‐014699) | BRCA1, BRCA2 or PALB2 mutated pancreatic cancer (NCT03140670) | |||
| Pancreatic cancer with BRCA mutations (NCT02042378) | ||||
| APE1 | TRC102 | Combination with pemetrexed in advanced solid tumors (NCT00692159) | (100) | |
| NER | RPA | HAMNO | HAMNO was shown to act synergistically with etoposide to kill cancer cells (UMSCC38 and UMSCC11B) in vitro and slow tumor growth in vivo | (101) |
| TDRL‐505 | TDRL‐505 prevented cell cycle progression and acted synergistically with cisplatin in non–small‐cell lung cancer (NSCLC) cells | (102) | ||
| MCI13E | MCI13E showed chemotherapeutic promise in ovarian and lung cancer cell lines when used in combination with cisplatin, or as a single agent | (43) | ||
| XPA | NERI01(AB‐00026258) | NERI01 significantly sensitized human colon cancer cells to UV irradiation | (103) | |
| XPF | F06/NERI02(NSC130813) | F06 was shown to act synergistically with cisplatin and mitomycin C in NSCLC cells and human colon cancer cells | (104) | |
| HR | Mre11 | Mirin | Mirin abolished the G2/M checkpoint and homology‐dependent repair in mammalian cells (U2OS, TOSA4) | (105) |
| RAD51 | IBR2 | IBR2 was shown to overcome imatinib resistance in chronic myeloid leukemia (CML) cells and murine models | (106) | |
| NHEJ | DNA‐PK | M3814 | Advanced solid tumors (NCT02516813) | |
| Locally advanced rectal cancer (NCT03770689) | ||||
| VX‐984 | Advanced solid tumors (NCT02644278) | |||
| CC‐115 | Castration‐resistant prostate cancer (NCT02833883) | |||
| DDR checkpoints | ATM | AZD0156 | Monotherapy or combination with other anticancer treatment in advanced solid tumors (NCT02588105) | |
| AZD1390 | Combination with radiation therapy in brain cancer (NCT03423628) | |||
| KU‐60019 | PTEN‐deficient breast cancer cells are sensitive to KU‐60019 when combined with cisplatin | (107) | ||
| TP53 mutant glioblastoma (GBM) cells are sensitive to KU‐60019 under the ionizing radiation | (108) | |||
| Combination with sunitinib, pazopanib, temsirolimus in human renal tumors (NCT03571438) | ||||
| Combination with avelumab in DDR‐deficient advanced solid tumors (NCT04266912) | ||||
| ATR | VX‐970 (M6620) | Combination with Irinotecan in TP53‐mutant gastric or gastroesophageal junction cancer (NCT03641313) | ||
| Advanced solid tumors (NCT03718091) | ||||
| AZD6738 | Combined AZD6738 and olaparib potentiates genome instability and cell death in ATM‐deficient cancer cells | (109) | ||
| Combination with olaparib in advanced solid tumors including ATM‐deficient/proficient gastric cancer, lung cancer, breast cancer (NCT02264678) | ||||
| Combination with olaparib in pancreatic cancer, renal cancer, urothelial cancer (NCT03682289) | ||||
| Combination with olaparib in gynecological cancers with ARID1A loss (NCT04065269) | ||||
| BAY1895344 | Advanced solid tumors and lymphoma (NCT03188965) | |||
| Combination with niraparib in DDR‐deficient advanced solid tumors (NCT04267939) | ||||
| CHK1 | Prexasertib (LY2606368) | Prexasertib synergizes with olaparib in triple‐negative breast cancer cells | (110) | |
| Small cell lung cancer (NCT02735980) | ||||
| BRCA1/2 mutation associated breast cancer, ovarian cancer and prostate cancer (NCT02203513) | ||||
| Combination with olaparib in advanced solid tumors (NCT03057145) | ||||
| Rabusertib (LY2603618) | Combination with gemcitabine in pancreatic cancer (NCT00839332) | (111) | ||
| Combination with pemetrexed/cisplatin in non–small‐cell lung cancer (NCT01139775) | (112) | |||
| CHK1/2 | AZD7762 | Monotherapy or combination with gemcitabine in advanced solid tumors (NCT00413686) | ||
| WEE1 | AZD1775 | Combination with gemcitabine and radiation therapy in pancreatic cancer (NCT02037230) | (113) | |
| Combination with gemcitabine and nab‐paclitaxel in pancreatic cancer (NCT02194829) | ||||
| Small cell lung cancer with MYC family (MYC, MYCN, MYCL) amplification or CDKN2A mutation combined with p53 mutation (NCT02688907) | ||||
| Combination with paclitaxel, in gastric cancer harboring p53 mutation (NCT02448329) | ||||
| Combination with carboplatin in p53 mutated ovarian cancer (NCT01164995) |