Table 2.

Main metabolic effects and clinical characteristics of metabolism-targeting drugs under clinical investigationa

DrugMetabolic effectsPotential clinical effectsRisks and side effectsOngoing trials (tumor types)
Metformin
  • – Reduced glycemia in hyperglycemics

  • – Reduced insulinemia in hyperglycemics

  • – Reduced FA and cholesterol synthesis in liver and tumor cells

  • – Inhibition of mTOR and protein synthesis

  • – Synergistic with CT, RT, or dietary interventions

  • – Lactic acidosis if poor liver, kidney, lung, and heart function

  • – Diarrhea

Lung: NCT02019979, NCT02285855, NCT02115464; Prostate: NCT02640534;Breast: NCT01310231; Endometrial: NCT02755844, NCT01797523; Ovarian: NCT02312661, NCT02122185; WDNETs: NCT02294006, NCT02823691
Aspirin
  • – Reduced glycemia in hyperglycemics

  • – Reduced FA and cholesterol synthesis in liver and tumor cells

  • – Inhibition of mTOR and protein synthesis

  • – Tumor growth inhibition

  • – Reduced systemic and peritumoral inflammation

  • – Synergistic with CT

  • – Reduced metastasis

  • – Gastrointestinal bleeding

  • – Liver and kidney damage

Prostate: NCT02420652; Colorectal: NCT02607072, NCT00565708; Breast: NCT02602938, NCT02804815; Lung: NCT01707823; Esophageal: NCT02326779
DCA
  • – Inhibition of aerobic glycolysis (PDK inhibition)

  • – Synergistic with RT or CT

  • – Toxic to tumors overexpressing PDK

  • – Synergistic with metformin

  • – Peripheral neuropathy

H&N: NCT01386632
Gossypol
  • – Inhibition of aerobic glycolysis (LDHA inhibition)

  • – Synergistic with metformin

  • – Fatigue

  • – Anemia

  • – Dyspnea

NSCLC: NCT01977209; B-CLL: NCT01003769
AZD3965
  • – Inhibition of aerobic glycolysis (MCT1 inhibition)

  • – Toxic to highly glycolytic tumors

  • – Unknown

Several advanced tumors: NCT01791595
CB-839
  • – Inhibition of glutamine metabolism

  • – Synergistic with CT or inhibitors of aerobic glycolysis

  • – Unknown

Breast, lung, renal: NCT02771626, NCT02071862;Leukemia: NCT02071927
ADI-PEG
  • – Degradation of circulating arginine

  • – Killing of ASS1-defective tumors

  • – Leukopenia

  • – Fatigue

Liver, lung, uveal melanoma, glioma, and mesothelioma: NCT02029690; Prostate and NSCLC: NCT01497925; Gastrointestinal: NCT02102022; Mesothelioma: NCT02709512
EGCG/green tea extracts
  • – Inhibition of FASN and de novo synthesis of FAs

  • – Inhibition of tumor cell proliferation

  • – Synergistic with CT

  • – Weight loss

  • – Loss of fatty tissue

Breast: NCT00949923; Urothelial: NCT01993966; SCLC: NCT01317953
Statins
  • – Inhibition of HMG-CoA reductase and de novo synthesis of cholesterol and isoprenoids

  • – Inhibition of tumor cell proliferation

  • – Synergistic with CT and inhibition of FA neosynthesis

  • – Myotoxicity

  • – Liver toxicity

Rectal: NCT02161822; NCT02569645; Prostate: NCT01992042; Breast: NCT02483871, NCT02416427; Bladder: NCT02360618
Rapalogs
  • – Inhibition of protein synthesis

  • – Activation of autophagy

  • – Inhibition of tumor cell proliferation

  • – Synergistic with metformin or glycolysis inhibitors

  • – Mucositis

  • – Fatigue

Breast, renal, and pancreatic: NCT02077933; Endometrial and ovarian: NCT02188550; WDNETs: NCT01648465, NCT02294006
  • Abbreviations: WDNET, well-differentiated neuroendocrine tumor; H&N, head and neck; NSCLC, non–small cell lung cancer; B-CLL, B-cell chronic lymphocytic leukemia; SCLC, small cell lung cancer; CT, chemotherapy; RT, radiotherapy.

  • aOnly the most representative ongoing studies are reported, and for each of them the ClinicalTrials.gov identifier is indicated.