Table 2.
Possible therapeutic strategies with DNA damaging agents and DNA damage repair (DDR) inhibitors in cancer therapy
| Cancer type | Drug name | Targeted gene | Trial | Therapeutic effects | Reference |
|---|---|---|---|---|---|
| Breast cancer | Olaparib | PARP inhibitor | Phase II trial | Olaparib yielded a high clinical response rate for therapy of triple negative breast cancer with HR deficiency | 560 |
| Cyclophosphamide | BRCA1/2, PALB2, BLM | Phase II trial | Over a 3-year follow-up, all patients were alive and disease-free survival was 87.1% | 561 | |
| Carboplatin | platinum compound | Phase II trial | The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer | 562 | |
| Talazoparib | PARP inhibitor | Randomized control, phase III | Compared to the physician’s choice of chemotherapy, Talazoparib didn’t improve final overall survival in BRCA-mutated HER2-negative advanced breast cancer | 563 | |
| Veliparib (ABT-888) | Randomized control, phase III | Veliparib yielded to a higher free survival time than placebo group in BRCA-mutated HER2-negative advanced breast cancer | 564 | ||
| Niraparib | PARP inhibitor | Open-Label Clinical Trial | Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations | 565 | |
| Iniparib | PARP inhibitor | Phase II trial | The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% and the rate of overall response from 32% to 52% | 566 | |
| AZD0156 | ATM inhibitor | Phase I study | AZD0156 enhances the tumor growth inhibitory effects of radiation treatment in vivo | 567 | |
| Prexasertib(LY2606368) | CHK1/2 inhibitor | Phase II trial | Prexasertib monotherapy had modest clinical efficacy in BRCAwt TNBC | 568 | |
| Ovarian cancer | Rucaparib | Randomized control, phase III | Rucaparib yielded a high clinical response rate for therapy of recurrent ovarian cancer with BRCA-mutant cohort, HR deficient cohort | 569 | |
| Niraparib | Randomized control, phase III | Niraparib yielded a long-term safety for maintenance therapy in patients with recurrent ovarian cancer | 570 | ||
| Cyclophosphamide | BRCA1/2, PALB2, BLM | Phase II nonrandomized trial | Oral cyclophosphamide was well tolerated and demonstrated clinical benefit in 25.0% of patients with recurrent ovarian cancer | 571 | |
| Olaparib | PARP inhibitor | Randomized control, phase III | Mean quality-adjusted progression-free survival (olaparib 29.75 months [95% CI 28.20–31.63] vs placebo 17.58 [15.05–20.18] | 572 | |
| Cisplatin | Alkylating agent | phase III | Cisplatin + Doxorubicin does not induce significant hepatic and renal toxicity and can be considered a valid therapeutic option in patients with advanced peritoneal disease | 573 | |
| Ceralasertib | Randomized control, phase II | Trial registration:NCT04239014 | 491 | ||
| Bladder cancer | Cisplatin | Alkylating agent | Phase II | Gemcitabine and cisplatin is an active, well-tolerated neoadjuvant regimen for the treatment of patients withmuscle-invasive bladder cancer | 574 |
| Mitomycin | Alkylating agent, | Phase II | Intravesical mitomycin C of a short-term schedule is safe and without additional toxicity compared with the weekly regimen | 575 | |
| Doxorubicin | topoisomerase II inhibitor | Phase III | Treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin results in a high response rate, less toxicity, and few dosing delays | 576 | |
| KU55933 | ATM inhibitor | Phase I | The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with DAB2IP gene defect | 577 | |
| CM-272 | DNMT1 inhibitor | Phase I | The antitumor effect is significantly improved when CM-272 is combined with anti-programmed cell death ligand 1, even in the absence of cisplatin | 578 | |
| Colon cancer | 5-fluorouracil | DSBs inductor | Phase II | Fluorouracil monotherapy combined with panitumumab was safely | 579 |
| Irinotecan | Topoisomerase I inhibitor | Phase II | S-1 plus irinotecan and oxaliplatin is feasible and efficacious for refractory mCRC patients | 580 | |
| Oxaliplatin | Alkylating agent | Phase II | S-1 plus oxaliplatinhas decreased the incidence of grade 2 neuropathyfrom 8.1 to 2.7% after 3 years of the therapyand survival rate was 73.9% | 581 | |
| Olaparib | PARP inhibitor | The lack of anti-tumor efficacy observed in this trial makes this combination of olaparib and irinotecanlittle interest for further clinical development | 582 | ||
| Glioblastoma | Temozolomide | Alkylating agent | Phase 1 | Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity | 583 |
| Lung cancer | Gossypol | Randomized control | Gossypol yielded to a better median progression-free survival and median overall survival rate than control placebo group | 584 | |
| Cisplatin | Alkylating agent | Phase II | Metronomic oral vinorelbine and tri-weekly cisplatin has a 66.2% overall response rate in non-small cell lung cancer | 585 | |
| Talazoparib | PARP inhibitor | Phase II | Median progression-free survival and overall survival were 2.4 months (95% CI, 1.5–2.8) and 5.2 months (95% CI, 4.0–10), respectively | 586 | |
| Olaparib | PARP inhibitor | Phase I/II trial | Combination of olaparib and temozolomide has median overall survival was 8.5 months (95% CI, 5.1–11.3) | 587 | |
| Leukemia | Doxorubicin | DSBs inductor | Phase II | Bortezomib, dexamethasone plus doxorubicin has a overall survival of 36.3 (95% CI, 25.6; -) months | 588 |
| Vorinostat | HDAC inhibitor | Phase II | Best overall response rate in phase II was 22% | 589 | |
| Talazoparib | PARP inhibitor | Talazoparib combined with NL101 had a strong synergistic effect in treating AML | 590 | ||
| Prexasertib | CHK1/2 inhibitor | Prexasertibincreases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia | 591 | ||
| Liver cancer | Cisplatin | Alkylating agent | Phase I/II | The overall median survival time of combination of 5-fluorouracil, mitoxantrone and cisplatin, is 11.3 months | 592 |
| Doxorubicin | Topoisomerase II inhibitor | Phase II | The overall median survival time was 8.6 months | 593 | |
| Cetuximab | Phase III | Median overall survival was 55·4 months (43.5–71.5) in the chemotherapy plus cetuximab group (HR 1.45, 1.02–2.05; p = 0·036) in patients with resectable colorectal liver metastasis | 594 | ||
| Capacitabine | Pro-drug of 5-fluorouracil/TS inhibitor | Phase III | Median overall survival was 51.1 months (95% CI 34.6–59.1) in the capecitabine group compared with 36.4 months (29.7–44.5) in the observation group | 595 | |
| Mitoxantrone | Topoisomerase II inhibitor | Phase I/II | The overall median survival time of combination of 5-fluorouracil, mitoxantrone and cisplatin, is 11.3 months | 592 | |
| Veliparib | PARP inhibitor | Phase II | The combination of temozolomide and veliparib is well tolerated in patients with advanced HCC | 596 | |
| Palbociclib | ATM inhibitor | Phase I/II | Antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 20% patients | 597 | |
| Non-Hodgkin Lymphoma | Cyclophosphamide | Alkylating agent | Phase II | The overall survival rate was 64% at 10 years | 598 |
| Doxorubicin | Topoisomerase inhibitor | Phase II | With a median follow-up of 48·7 months, the 4-year progression-free and overall survivals were 83% and 93% | 599 | |
| Olaparib | PARP inhibitor | Olaparib is highly radiosensitizing agents when used before external beam radiation and ¹³¹I-tositumomab. | 600 | ||
| Prostate Cancer | Carboplatin | Platinum compound | Phase II | Combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side-effect profile | 601 |
| Cisplatin | Alkylating agents | Phase II | Cisplatin plus prednisone appears to represent an active regimen in docetaxel-refractory castration-resistant prostate cancer with an acceptable toxicity profile | 602 | |
| Nedisertib | DNA-PKcs | Randomized control, phase II | No Study Results Posted on ClinicalTrials.gov for this Study | https://clinicaltrials.gov/ | |
| Pancreas cancer | 5-fluorouracil | DSBs inductor | Phase I/II | The combination of veliparib and Oxaliplatin was tolerable, the objective response rate overall was 26% | 603 |
| Oxaliplatin | Platinum compound | Phase II | Median overall survival, progression-free survival, and response rates were 7.6 months (95% CI 6.0–10.7), 4.0 months (95% CI 2.0–4.6), and 26.7% (95% CI 14.6–41.9), respectively | 604 | |
| Irinotecan | Topoisomerase I inhibitor | Estimated one-year overall survival rates were 26% with Liposomal irinotecan plus 5-fluorouracil and leucovorin | 605 | ||
| Olaparib | PARP inhibitor | Phase I | Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600 mg/m(2) is tolerated in advanced solid tumor patients, with no unmanageable/unexpected toxicities | 606 |