Table 3 Clinical trials on metabolic targets in PLC

Glycolysis

MCT1

AZD3965

NCT01791595

Phase 1 (Completed)

Advanced cancer [168]

GLUT1

Aspirin

Lamivudine

NCT01936233

Phase 3

(Unknown)

Liver cancer after radical surgery

PDK

Dichloroacetate

NCT00566410

Phase 1 (Completed)

Recurrent and/or metastatic solid tumors [169]

TCA cycle

Mitochondrial complex I

Metformin

Celebrex

NCT03184493

Phase 3 (Unknown)

HCC recurrence after hepatic resection [170, 171]

Sirolimus

NCT02145559

Phase 1 (Completed)

Advanced solid tumors

Vitamin C

NCT04033107

Phase 2

(Recruiting)

Malignant tumors

Sorafenib

NCT02672488

Phase 3 (Unknown)

Advanced HCC

Chloroquine

NCT02496741

Phase 1b (Completed)

IDH1/2-mutated malignant tumors (including CCA)

IDH1/2

AG120 (Ivosidenib)

NCT02989857

NCT06081829

NCT05876754

Favorable OS benefit (Phase 3 completed and Phase 2/3b recruiting)

Previously treated patients with nonresectable or metastatic CCA

/Advanced solid tumors (including CCA) [172,173,174]

Gemcitabine and cisplatin

NCT04088188

Phase 1 (Active)

Nivolumab

Ipilimumab

NCT05921760

Phase 1/2 (Recruiting)

NCT02073994

Phase 1 (Active)

FAO and cholesterol

metabolism

HMG-CoA reductase

Pravastatin

Sorafenib

NCT01075555

NCT01357486

NCT01418729

NCT01903694

Unfavorable OS benefit (Phase 3/2/2/3, completed)

HCC [175−176]

Atorvastatin

NCT03024684

Phase 4 (Recruiting)

HCC recurrence after curative treatment

Simvastatin

NCT02968810

Phase 2

(Active)

HCC in patients with cirrhosis

Statin

NCT03490461

Observational

HCC recurrence after liver transplantation

SPHK2

ABC294640

Hydroxychloroquine

NCT03377179

Phase 2 (Completed)

Advanced, unresectable CCA [178]

NCT01488513

Phase 1 (Completed)

Advanced solid tumor (including HCC)

Amino acid metabolism

Glutamine

DRP-104

Durvalumab

NCT06027086

Phase 1b/2 (Not yet recruiting)

Advanced fibrolamellar HCC

Glutaminase

CB-839

Standard chemotherapy

NCT02071862

Phase 1

(Completed)

Advanced and/or treatment-refractory solid tumors