Table 3:

Emerging Treatments for Prostate Cancer that Target Metabolism.

Compound	Target	Preclinical Model	Effect	Reference (PMID)
Oxidative Phosphorylation
Metformin	ETC Complex I, Pleiotropic	Multiple preclinical studies, retrospective analyses, and multiple ongoing clinical trials	Inhibits tumor proliferation in multiple tumor types, potential survival benefit in large retrospective prostate tumor cohort, ongoing clinical trials.	29940252 30150001 28444639 29075616 27746051
IACS-010759	ETC Complex I	Brain cancer and acute myeloid leukemia	Inhibits proliferation, depletes macromolecule pools, and induces apoptosis. In vitro and in vivo data, ongoing clinical trial.	29892070
MSDC-0160	Mitochondrial Pyruvate Carrier	Hormoneresponsive and castrate-resistant AR-positive prostate cancer	Decreases mitochondrial oxygen consumption, depletes TCA intermediates, inhibits lipogenesis, activates integrated stress response, suppresses cell proliferation and tumor growth. In vitro and in vivo data.	https://doi.org/10.1038/s42255-018-0002-y
Lipogenesis
IPI-9119	FASN	Hormone responsive and castrate resistant AR positive prostate cancer	Antagonizes growth through metabolic reprogramming and results in reduced protein expression and transcriptional activity of full-length AR and splice variant AR-V7. In vitro and in vivo data.	30578319
ND-646	Acetyl-CoA Carboxylase	Non-small-cell lung cancer	Suppresses fatty acid synthesis, inhibits tumor growth in KRAS p53 and KRAS Lkb1 autochthonous mouse models.	27643638
MT 63–78	AMPK	Hormone responsive and castrate resistant prostate cancer. AR positive and AR negative.	Inhibits cell proliferation, induces mitotic arrest and apoptosis. Constitutively activates AMPK and suppresses lipogenesis. In vitro and in vivo data.	24497570
Fatostatin	SREBP-SCAP	Metastatic and non-metastatic autochthonous models of mouse prostate cancer	Inhibits lipogenesis, blocks tumor growth and metastatic spread.	29335545
Statins	HMG-CR	Multiple preclinical studies, retrospective analyses, and multiple ongoing clinical trials	Inhibits tumor proliferation in multiple tumor types, potential survival benefit in large retrospective prostate tumor cohort, ongoing clinical trials.	28806117 20377474 17179483
Glutaminolysis
CB839	Glutaminase	triple-negative breast cancer, lung cancer	Antiproliferative activity and decreased glutamine consumption in triple negative breast cancer models. In vitro and in vivo data. Radiosensitization in lung tumor models. In vitro and in vivo data	24523301 30557074
V-9302	SLC1A5/ASCT2	Multiple cell line models, colon cancer xenografts	Attenuates proliferation, increases apoptosis and oxidative stress. In vitro and in vivo data.	29334372
Autophagy
Chloroquine	Lysosomal function	Multiple preclinical studies and multiple ongoing clinical trials	Inhibits tumor proliferation and survival in multiple tumor types, ongoing clinical trials.	25134829 22241682 23670050 27322458