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Table 1 Antitumor agents that promote mitotic catastrophe: potential applications and clinical trials

From: A link between mitotic defects and mitotic catastrophe: detection and cell fate

Inhibitor

Mechanism of action

Tumor types for treatment

Potential applications and clinical trials

ATR inhibitor AZD6738

ATR blockade leads to destruction of inhibited replication forks with the formation of breaks in the replicated sister chromatids that can be fused by deletions and aberrant chromosomal translocations

Renal cell carcinoma, urothelial carcinoma, all pancreatic cancers, endometrial cancer

Phase 2 clinical trial: AZD6738 alone and in combination with the PARP-inhibitor olaparib (NCT03682289) [81]

DNA-PK inhibitor NU7026

Increased polyploidy and mitotic catastrophe after low dose irradiation

Negative changes in the NHEJ system in a cell-cycle-dependent manner

Cervical cancer

Preclinical study [60]

Non-small cell lung cancer

Preclinical study [61]

DNA-PK inhibitor M3814

Block repair of radiation-induced double-stranded breaks and promote p53-dependent mitotic catastrophe

Ovarian cancer

Preclinical study [62]

Fibrosarcoma and lung cancer

Preclinical study [63]

DNA-PK inhibitor AZD7648

This inhibitor in combination with the PARP inhibitor olaparib, doxorubicin, or radiotherapy causes prolonged arrest of the cell cycle in the G2/M transition, accumulation of micronuclei, and chromosomal aberrations that are indicative of mitotic catastrophe

Ovarian cancer

Preclinical study [64]

HER2 + , HR + and HER2-negative, triple-negative breast cancer

Phase 1–2 clinical trial (NCT03907969) [82]

HPV-negative head and neck cancer squamous carcinoma

Preclinical study [65]

Mps1/TTK kinase inhibitor

CFI-402257

Disrupt chromosome segregation and block metaphase

Advanced/metastatic HER2-negative breast cancer

Phase 1b clinical trial in combination with paclitaxel (NCT03568422) [67]