Table 2 Selection of drugs targeting p53-related networks in clinical trials as indicated in the ClinicalTrials.gov database.

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

–

–