Table 3.

Metabolic inhibitors in combination with chemotherapy.

Targeted Metabolism	Metabolic Inhibitor	Chemotherapy	Preclinical Data	Clinical Data
Glycolysis	3-BP (HK2 inhibitor)	Platinum drugs (cisplatin, oxaliplatin)	CRC [250]
		5-fluorouracil	CRC [251]
		Doxorubicin	Neuroblastoma [252]
		Daunorubicin, mitoxantrone, doxorubicin	MM, AML, HCC [253]
	2-DG	Etoposide	Lymphoma [254]
		Doxorubicin + radiotherapy	Breast [255]
		Doxorubicin, paclitaxel Docetaxel	Osteosarcoma, NSCLC [256]	Phase I—various [257]
	PKM2 modulation	Cisplatin	Cervical [258] Bladder [259]
		Docetaxel	Lung [260]
Glutaminolysis	CB-839	Paclitaxel	TNBC [200]	Phase I—TNBC (NCT02071862) [261] Phase II—TNBC (NCT03057600) [262]
		Docetaxel		Phase I—NSCLC (NCT02071862)
		Cepecitabine		Phase I/II—solid tumours (NCT02861300)
Mitochondrial Metabolism	CPI-613/Devimistat (PDH and α-KG dehydrogenase complex inhibitor)	FOLFIRINOX (oxaliplain, folinic acid, irinotecan, fluorouracil)		Phase I—PDAC (NCT01835041) [263] Phase III—PDAC (AVENGER 500 trial, NCT03504423)
		Cytarabine + mitoxantrone		Phase III—AML (ARMADA 2000 trial, NCT03504410) [264]
	Metformin	Doxorubicin	Prostate, lung [265]
		Carboplatin	NSCLC [57]
		5-fluorouracil		Phase II—CRC (NCT01941953) [266]
		Irinotecan		Phase II—CRC (NCT01930864)
		Neo-adjuvant chemotherapy (TCH+P)		Phase II—HER2-positive breast (HERMET trial, NCT03238495)
		Radiotherapy		Phase II—prostate (NCT02945813)
		Enzalutamide		Phase II—prostate (IMPROVE trial, NCT02640534)
	IACS-010759 (complex I inhibitor)	Cytarabine + doxorubicin	AML [267]
	OPB-111077	Bendamustine + rituximab		Phase I—diffuse large B cell lymphoma (DLBCL) (NCT04049825)
	Dicholoroacetate (PDK2 inhibitor)	Paclitaxel	NSCLC [268]
		5-fluorouracil	CRC [269]
Other enzymes	CB-1158/INCB001158 (Arg1 inhibitor)	Chemotherapy		Phase I/II—solid tumours (NCT03314935)
	Indoximod/1-methyl-d-tryptophan (IDO1 inhibitor)	Taxane chemotherapy		Phase II—breast (NCT01792050)
		Gemcitabine		Phase I/II—PDAC (NCT02077881)