Table 1 Overview of therapeutic agents to which cells with mutated or knocked down IDH1/2 are sensitized

From: Wild-type and mutated IDH1/2 enzymes and therapy responses

Agent	IDH1/IDH2	Model or patient population	Protection by IDH1/2^MUT inhibitor?	References
Irradiation	IDH1^WT/R132H isogenic	HCT116 colorectal cancer cells; U251 glioblastoma cells; HeLa cells, murine HSCs	Yes	[29, 74, 75]
	IDH1^R132H IDH2^R172K overexpression	U87 and U373 glioblastoma cells	No	[62]
	IDH1^R132H and IDH2^R140Q endogenous	Primary human AML cells	No	[75]
	IDH1 knockdown	U87 glioblastoma cells in vivo, U138 and A172 glioblastoma cells	N/A	[63]
Chemotherapy
5-Fluoruracil	IDH1^R132H overexpression	U87 glioblastoma cells	No	[66]
Busulfan	IDH1^R132H overexpression	U87 glioblastoma cells	No	[81]
Carmustine (BCNU)	IDH1^R132C/H/L overexpression and IDH1 knockdown	LN229 glioblastoma cells and HEK293 cells	No	[41]
Cisplatin (CDDP)	IDH1^R132H overexpression	U87 and U251 glioblastoma cells	No	[64]
Cisplatin (CDDP)	IDH1^WT/R132H isogenic	HeLa cells	No	[75]
Daunorubicin	IDH1^WT/R132H isogenic	Murine HSCs	No	[74]
Gemcitabine	IDH1 knockdown	Mia pancreatic cancer cells	N/A	[73]
Lomustine (CCNU)	IDH1^R132H overexpression	U87 glioblastoma cells	No	[81]
Procarbazine, lomustine (CCNU) and vincristine (PCV)	IDH1^MUT endogenous	WHO grade II and III glioma patients	No	[21, 22]
Temozolomide	IDH1^R132H overexpression	U87 and U251 glioblastoma cells in vivo, UACC257 melanoma cells	No	[31, 60]
Temozolomide	IDH1^MUT endogenous	Primary glioma neurospheres, HT1080 chondrosarcoma cells in vivo, low-grade glioma patients	No	[26, 88]
Targeted therapy
ABT-263	IDH1^R132H overexpression	U87 and T98G glioblastoma cells, glioma stem-like cells in vitro, U87 glioblastoma cells in vivo	No	[51]
	IDH1^WT/R132H isogenic	HCT116 colorectal cancer cells in vitro and in vivo	No	[51]
	IDH1^R132H endogenous	Patient-derived glioblastoma xenograft	No	[51]
All-trans retinoic acid	IDH1/2^MUT endogenous	Primary AML cells in vitro and in vivo	No	[51]
All-trans retinoic acid	IDH1^R132H overexpression	HL60 APL cells in vitro and MOLM14 AML cells in vitro and in vivo	Yes	[61]
Berzosertib	IDH1^WT/R132H isogenic	HeLa cells	No	[75]
Erlotinib	IDH1 knockdown	Glioma stem cells	N/A	[48]
Dasatinib	IDH1^R132C, IDH1^R132S, IDH1^R132V endogenous	ICC cells in vitro and in vivo	No	[53]
Dasatinib	IDH2^R172K overexpression	Murine intrahepatic cholangiocarcoma cells in vitro and in vivo	No	[53]
FK866 and GMX1778	IDH1/2^MUT endogenous	Primary glioma neurospheres, SW1353 chondrosarcoma cells, HT1080 chondrosarcoma cells in vivo	No	[52, 88]
FK866 and GMX1778	IDH1^R132H overexpression	U87 glioblastoma cells in vivo, UACC257 melanoma cells	No	[52, 88]
Niraparib (MK-4827)	IDH1^WT/R132H isogenic	HeLa cells	No	[75]
Rucaparib	IDH1^WT/R132H isogenic	HeLa cells	No	[75]
Olaparib	IDH1^WT/R132H isogenic	HCT116 colorectal cancer in vivo, HeLa cells in vivo, THP-1 AML cells, HT1080 chondrosarcoma in vivo, primary glioma neurospheres	Yes	[75, 88]
Sacratinib	IDH1^R132C, IDH1^R132S, IDH1^R132V endogenous	ICC cells in vitro	No	[53]
Sacratinib	IDH2^R172K overexpression	Murine ICC cells in vitro	No	[53]
Talazoparib (BMN-673)	IDH1^WT/R132H isogenic	HCT116 colorectal cancer, THP-1 AML cells, HeLa cells	Yes	[75]
Talazoparib (BMN-673)	IDH1^WT/R132H endogenous	Primary human glioma cells	No	[75]
Venetoclax (ABT-199)	IDH1^R132H, IDH2^R140Q, IDH2^R172K overexpression	THP-1 acute myeloid leukemia cells	Yes	[49]
	IDH1^MUT endogenous	Primary human AML cells	No	[49]
	IDH1^R132, IDH2^R140, IDH2^R172K endogenous	AML patients	No	[50]
Metabolic therapy
Aminooxyacetic acid	IDH1^R132H overexpression and IDH1 knockdown	LN229 glioblastoma cells	No	[41]
BPTES	IDH1^R132H overexpression	D54 glioblastoma cells	No	[42]
BPTES	IDH1^R132C/G/H, IDH2^R140Q endogenous	Primary AML cells	No	[40]
Metformin	IDH1^WT/R132H isogenic	HCT116 colorectal cancer cells	Yes	[29, 36]
Phenformin	IDH1^WT/R132H isogenic	HCT116 colorectal cancer cells	No	[37]
Zaprinast	IDH1^R132H overexpression	Normal human astrocytes	No	[39]

ABT-263 and venetoclax are BH3 mimetics, of which venetoclax is more selective towards BCL-2 inhibition whereas ABT-263 inhibits both BCL-2 and BCL-XL, all-trans retinoic acid induces differentiation by promoting retinoic acid-responsive gene expression; berzosertib is an ATR/ATM inhibitor; dasatinib and sacratinib are multikinase inhibitors, FK866 and GMX1778 are NAMPT inhibitors; niraparib, rucaparib, olaparib, and talazoparib are PARP inhibitors. AML acute myeloid leukemia, APL acute promyelocytic leukemia, ICC intrahepatic cholangiocarcinoma, HSC hematopoietic stem cell, IDH1/2^MUT mutated IDH1/2

Back to article page

Table 1 Overview of therapeutic agents to which cells with mutated or knocked down IDH1/2 are sensitized

Search

Quick links