Table 4.

Therapeutic approaches against ATR and ATM in hematologic malignancies

Targets	Drugs	Type of malignancy	Highlights	Ref
ATM	KU-55933	Jurkat cells	Impairment of the auto-phosphorylation of ATM and inhibition of H2AX phosphorylation	[203, 225]
		MV4-11 cells (AML cell line)	ATM inhibition radiosensitized MV4-11 leukemia cells	[182]
		P39 and MOLM-13 cell lines (MDS cell lines)	ATM inhibition increase radiosensitization of MDS cells	[182]
		EBV-driven Burkitt lymphoma cells	Inhibition of EBV replication through inhibition of KAP1 phosphorylation	[205]
		Ramos cells	Prevention of ATM auto-phosphorylation and potentiation of etoposide-induced apoptosis	[226]
		Cisplatin-resistant MCL cell line (JeKo-1/DDP)	Enhanced cisplatin-induced DNA damage	[206]
		HCL cell line MLMA	Induction of apoptosis through inhibiting NF-κB pathway	[207]
	KU-59403	Jurkat cells	Showing higher potency, tissue distribution, and efficacy over KU-55933	[225]
	AZD0156	AML	exhibits therapeutic potential in a mouse model of MLL-rearranged AML	[227]
	KU-60019	Human B cell lymphoma cell lines, lymphoblastoid cell lines, and myeloma lines	KU-60019 potentiates bendamustine activity	[212]
		MCL cell lines	KU60019 synergizes the antineoplastic effect of romidepsin	[228]
	Caffeine (Inhibitor of both ATM and ATR)	K562 leukemia cells	Caffeine sensitises the cells to genotoxic modalities, particularly irradiation	[229]
		Lymphoma patients	Potentiated chemotherapy and induction of complete remission	[213]
ATR	VE-821	APL cells	Increase of radio sensitization	[217, 218]
		MM cells	Significantly increased apoptosis of MM cells in combination with KU-55933	[218]
		TP53-mutant MM cell lines	As monotherapy alone and in combination with DNA damaging agents, CX5461 or melphalan	[230]
	VE-822 (VX-970)	AML	Increase antileukemic activity of hydroxyurea and gemcitabine in AML mouse model	[220]
	AZD6738	CLL patients	ATR inhibition induces synthetic lethality in TP53- or ATM-defective CLL cells	[221]
		ATM-deficient DLBCL model	Combination therapy with carboplatin, bendamustine, and cyclophosphamide	[219]
		Relapsed/refractory high-risk CLL patients	A phase I clinical trial of AZD6738 in combination with acalabrutinib [Trial identifier: NCT03328273]	-
	BAY1895344	MCL models	Synergistic anti-tumor activity in combination with DNA damage-inducing chemotherapy or radiation therapy	[224]
	AZ20	AML-MLL murine model	Strong cytotoxic effects in vitro and in murine models, irrespective of p53 status	[231]
	WO2010/073034	ATM-deficient MCL	Promising results both in vitro and in vivo models	[223]