Table 2.
Selection of drugs targeting p53-related networks in clinical trials as indicated in the ClinicalTrials.gov database.
| Drug name | Target | Effect of p53 | p53-dependent phenotype in tested cancer cells | Clinical stage (status) | Combination | Diseases | NCT # |
|---|---|---|---|---|---|---|---|
| APR-246 | Mutant p53 | Restores wild-type functions | Apoptosis178 | Phase 2 (completed) | Azacitidine | TP53-mutant AML | NCT03931291 |
| Phase 3 (completed) | Azacitidine | TP53-mutant myelodysplastic syndromes | NCT03745716 | ||||
| Phase 2 (completed) | PLD | High-grade serous ovarian cancer | NCT03268382 | ||||
| COTI-2 | Restores wild-type functions | Apoptosis and senescence in HNSCC179 | Phase 1 | Cisplatin |
Gynecological tumors, head and neck squamous cell carcinoma |
– | |
| Nedisertib (M3814, peposertib) | DNA-PK | Induces p53 | Apoptosis in AML180 | Phase 1 (Recruiting) |
Radiation Temozolomide |
Glioblastoma | NCT04555577 |
| Phase 1 (Recruiting) | PLD | Ovarian cancer | NCT04092270 | ||||
| – | – | – | Phase 1 (completed) | PLD | Advanced solid tumor | – | |
| – | – | – | Phase 1 | Enzalutamide | Prostate cancer | – | |
| – | – | – | Phase 2 | Prexasertib | Triple-negative breast cancer | – | |
| – | – | – |
Phase 1, Phase 2 |
PLD | Advanced malignancies | – | |
| RG7388 (Idasanutlin) | Hdm2 | Stabilizes/activates p53 | Apoptosis of osteosarcoma cell line181 | Phase 1, Phase 2 (recruiting) | Venetoclax, other chemotherapies |
AML, ALL Neuroblastoma Solid tumors |
– |
| DS-3032b (Milademetan) | Stabilizes/activates p53 | Apoptosis182 | Phase 1, Phase 2 (completed) | Cytarabine, Venetoclax | AML | – | |
| – | Stabilizes/activates p53 | Apoptosis183 | Phase 2, Phase 3 (recruiting) | Doxorubicin | Liposarcoma | – | |
| AMG-232 (Navtemadlin) | Stabilizes/activates p53 |
Apoptosis of ALL cells184 Cell growth inhibition and apoptosis185 |
Phase 1 (recruiting) | Cytarabine, Idarubicin hydrochloride | AML | – | |
| APG-115 | Stabilizes/activates p53 | Cell cycle arrest and apoptosis in AML186 | Phase 2 (recruiting) | – | T-prolymphocytic leukemia | – | |
| CGM097 | Stabilizes/activates p53 | Cell cycle arrest and apoptosis in neuroblastoma187 | Phase 1 (completed) | – | Solid tumors | – | |
| – | ATM | – | – | Phase 1 | Olaparib, irinotecan, fluorouracil, folinic Acid | Advanced solid tumors | – |
| – | – | – | Phase 1 | Radiation | Brain tumor | – | |
| – | ATR | – | – | Phase 1 (recruiting) | Irinotecan hydrochloride | Solid tumors | NCT02595931 |
| Phase 2 (completed) | Solid tumorsLeiomyosarcomaOsteosarcoma | NCT03718091 | |||||
| – | – | – | Phase 1 (recruiting) | Niraparib |
Advanced solid tumors Ovarian cancer |
– | |
| – | CHK1 | – | – | Phase 1 (completed) | Gemcitabine | Solid tumors | – |
| MK-8776 (SCH 900776) | – | – | Phase 1 (completed) | Gemcitabine |
Hodgkin disease lymphoma, non-Hodgkin |
NCT00779584 | |
| LY2606368 (Prexasertib) | – | – | Phase 1 (completed) | – | Advanced cancer | NCT02778126 | |
| Phase 2 (completed) | Small-cell lung cancer | NCT02735980 | |||||
| Phase 2 (completed) | Ovarian cancerBreast cancerProstate cancer | NCT02203513 | |||||
| SRA737 | – | – | Phase 1/2 (completed) | – |
Advanced solid tumors Non-Hodgkin lymphoma |
NCT02797964 | |
| Phase 1 | Gemcitabine, Cisplatin | Advanced solid tumors | NCT02797977 | ||||
| Phase 2 (completed) | Gemcitabine | – | – |
PLD pegylated liposomal doxorubicin hydrochloride, AML acute myeloid leukemia, ALL acute lymphocytic leukemia, HNSCC head and neck squamous cell carcinoma.