Table 1.

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

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]