Table 3.

Summary of the frequency, intensity, duration, drug concentration, and the effect of TTFields combined drugs on various tumor cells.

Cancer type	Cell	Drug	Concentration	TTFields parameters	Time and effect	Ref.
Ovarian cancer	A2780, OVCAR3, CAOV-3	Paclitaxel	0–100 nM	200 kHz,2.7 V/cm	72 h CI A2780:1.03, OVCAR3:0.81, CAOV-3:0.86.	[37]
MPM	MSTO-211H, NCI-H2052	Cisplatin	1–10,000 nM	150 kHz, 1 V/cm	Pemetrexed+TTFields vs. Cisplatin+TTFields: additive vs. synergistical effect.	[28]
		Pemetrexed	1–100 nM		Cisplatin+TTFields: Apoptosis↑
					Triple therapy (two drugs+TTFields): proliferation and clonal formation↓
Lung cancer	Gefitinib-resistant PC-9GR, H1975 cells	Osimertinib	0.5 μM	1 V/cm	Proliferation↑, cell death, apoptosis↓	[29]
					TTFields attenuates the inhibitory effect of Osimertinib
	HCC827	Erlotinib	0–20 nM	150 kHz,1.75 V/cm	72 h: Proliferation and clonal formation↓	[34]
	H1299, LLC1, HTB-182, KLN205	Pemetrexed	0–0.1 nM	150 kHz,1.75 V/cm	72 h: Proliferation and clonal formation↓	[34]
		Paclitaxel	0–100 nM
		Cisplatin	0–10 nM
	H157, H4006, A549, H1299	Cisplatin	Cisplatin PIC25 (μM) : H157 1, H4006 0.75, A549 2, H1299 = 2.	100-200 kHz	Olaparib+IR + TTFields:CI>1.	[22]
		Olaparib	Olaparib 0–40 μM		Olaparib+IR, Olaparib+TTFields:CI ≈ 1.
Liver cancer	Huh7	Doxorubicin	0–10 µM	120 kHz, 1 Vpp	72 h: therapeutic effect↑	[38]
Glioma	LN-18, LN-229, T-325, ZH-161	TMZ	5 μM-200 μM	2 V/cm	24 h: LN-229, ZH-161: sensitization	[20]
	U118	Dacarbazine	0-100 mM	150 kHz, 1.75 V/cm	72 h: IC50: Dacarbazine 6.4 mM→0.023 mM, Paclitaxel 5 nM→0.005 nM, Doxorubicin 0.04 μM → 0.002 μM, Cyclophosphamide 6.6 mM→0.044 mM.	[31]
					DRI: Dacarbazine 175, Paclitaxel 316, Doxorubicin 23, Cyclophosphamide 152
	U373	Thymidine	2 mM	200 kHz	For G1/S blocked cells, proliferation, clonal formation, DNA damage and apoptosis=	[62]
	U373, U87	Sorafenib	5 μM	150 kHz, 0.9 V/cm	48 h: proliferation ↓ , cell death ↑ .	[26, 32]
					STAT3 expression ↓ . Knocking down STAT3: TTFields effect↑
					24 h: S phase, migration, invasion and angiogenesis↓
					48 h: clonal formation ↓ , apoptosis, autophagy, ROS ↑
	U-87 MG, U-138 MG, U-343 MG	MPS1-IN-3	4 µM	200 kHz, 1.7 V/cm	U-87 MG, GaMG: 72 h:proliferation ↓ .	[49]
					U-87 MG, 72 h: abnormal nuclei, G2/M, apoptosis ↑ .
					MPS1-IN-3 prolongs TTFields effect
	U87-MG, KNS42, SF188	Paclitaxel	High vs Low concentration	130 kHz, 10 V, 450 μs	Synergistically effect.	[45]
		Mebendazole			SubG0↑
GBM	KR158-luc	TMZ	300 µM	200 kHz	72 h: adaptive immune=	[69]
	Patient-derived glioblastoma stem cell-like cells (GSCs)	TMZ	1.5 μM-160 μM	200 kHz, 1 V/cm	8 days: same inhibitory efficacy in two cell types (MGMT expression + /-).	[54]
	U251-MG, MZ-54	Dexamethasone	65 μM	1.48–1.41 V/cm	48 h: sensitization.	[44]
					Dexamethasone: decrease IR induced-effect but does not affect TTFields induced-effect
					Dexamethasone+TTFields: PFS and OS =
	U87-MG, GBM2, GBM39	Withaferin A	0–0.1uM	200 kHz, 4 V/cm 2.5 V/cm	50 kHz vs. 200 kHz, 500 kHz: no sensitization vs. sensitization. Intensity dependent	[36]
Colonic cancer	HCT116	5-FU	5 µmol/L	0.9–1.2 V/cm	48 h: sensitization.	[30]
					Proliferation, clonal formation, migration, invasion↓
					Autophagy, apoptosis, organoid cell death↑
Cervical cancer	HeLa	Doxorubicin	0–10 µM	120 kHz, 1 Vpp	72 h: therapeutic effect↑	[38]
Breast cancer	EmtR1 cells, MCF-7/Mx, MDA-MB-231/Dox cells	Doxorubicin	0.04–0.6 μM,	150 kHz, 1.75 V/cm	TTFields+chemotherapy 72 h: Same efficacy in WT cell and drug-resistant cell. DRI: Doxorubicin 105-250 vs. Paclitaxel 815- >10,000	[27]
		Paclitaxel	5 nM–0.1 μM
	JIMT-1,BT-474	Trastuzumab	5 μM	–	72 h: Synergistical effect, clonal formation ↓ , apoptosis↑	[33]
	MDA-MB-231	Doxorubicin	IC50 = 0.31 μM	150 kHz, 4 V/cm	Synergistical effect	[36]
	MDA-MB-231	Doxorubicin, Paclitaxel, Cyclophosphamide	0–10 μM, 0–1000 nM, 0–100 mM	150 kHz, 1.75 V/cm	72 h IC50: Doxorubicin 0.04 μM → 0.002 μM, Paclitaxel 5.00 nM→0.005 nM, Cyclophosphamide 6.60 mM→0.044 mM.	[31]
					24 h treatment then quit for 48 h: Control and the chemotherapy group vs. Combined group: cell proliferation recovered rapidly vs. did not recover.
Pancreatic cancer	PC-1.0 (hamster), AsPC-1	Gemcitabine	–	150 kHz, 2.9 ± 0.2 V/cm	Therapeutic effect↑	[35]
		Irinotecan
		5-FU
		Paclitaxel
Liver cancer	Huh7	Doxorubicin	0–10 µM	120 kHz, 1 Vpp	72 h: therapeutic effect↑	[38]

↑ up-regulate,↓ down-regulate, = unchanged.

5-FU 5-Fluorouracil, WT wide type, DRI dose reduction index, IC50 half maximal inhibitory concentration, CI combination index, TMZ Temozolomide, STAT3 signal transducer and activator of transcription 3, MGMT O6 -methylguanine-DNA methyltransferase, OS overall survival, PFS progression-free survival, MDA-MB-231/Dox cells doxorubicin resistant MDA-MB-231 cells, EmtR1 cells AA8 cells- Emetine-resistant sub-lines, MCF-7/Mx MCF-7 cells Mitoxantrone-resistant sub-lines, Vs versus.