Table 3.

Pre-clinical studies on PARP1 and DNA-PK inhibitors against hematologic malignancies

Target	Inhibitors	Type of malignancy	Highlights	Ref
PARP1	Olaparib (AZD2281, MK-7339)	MCL and MLL-AF9 rearranged Leukemia cells	Higher sensitivity of double-deficient ATM/p53 MCL cells, compared to mono-deficient MCL cells in ATM	[106]
	AG14361	MCL cells	Enhanced topotecan-induced apoptosis independent of TP53 status	[151]
	PJ-34	Patient-derived ATLL cells	p53-mediated caspase 3-dependent apoptosis	[155]
		HL60, MOLT4, and K562 human leukemia cell lines	Synergistic effect in combination with histone deacetylase inhibitor, vorinostat	[156]
	BMN-673 (talazoparib)	Patient-derived CLL samples	Inhibited the proliferation of CLL cells independently of p53/ATM function	[158]
		Primary AML samples AML mouse models	Enhanced apoptosis in combination with decitabine	[166]
	Veliparib (ABT-888)	Patients with relapsed/refractory lymphoma and MM	Enhances the cytotoxicity of bendamustine and rituximab	[161]
		MM cells MM xenografts in SCID mice	Combined treatment with CDK inhibitor dinaciclib resulted in synthetic lethality of MM cells	[162]
		Acute leukemia, high-risk MPNs	Promising results in Combined treatment with topotecan and carboplatin in phase I study	[164]
	P10	Human leukemic cell line Nalm6	Induction of G2/M arrest and accumulation of DNA damage	[168]
DNA-PK	Wortmannin	Human leukemia cells	Sonolisib (PX-866) is Irreversible wortmannin analogue PWT-458 is PEGylated derivative of wortmannin	[193, 194]
	NU7026	Primary CLL cells	Synergistic effects with chlorambucil	[195]
	CC-115	CLL, NHL, and MM	Phase I clinical trial A dual inhibitor of DNA-PK and mTOR	[177, 196]
	IC86621	NHL and HL	Synergistic effects with bleomycin and etoposide	[183]
	CC-122 (Avadomide)	NHL and MM	Phase I clinical trial	[178, 197]
	NU7441	Pre-B ALL cells	Increase of chemosensitivity to doxorubicin	[198]
	OK-1035	L5178Y cells (lymphoma cell line)	Preclinical testing	[199]
	Dbait (AsiDNA or DT01)	Lymphoma and leukemia cells	32 bp double-stranded DNA fragment that mimics DNA lesion and traps DNA repair enzymes A dual inhibitor of DNA-PK and PARP1	[191]
	GRN163L (Imetelstat)	CLL	Imetelstat sensitizes primary CLL lymphocytes to fludarabine A dual inhibitor of DNA-PK and telomerase	[192]