Table 1 |.
Metabolic targets for metastasis prevention and treatment discussed in this Review
| Target | Cancer type | Investigated metastatic side | Model | Targeting strategy | Effect on primary tumour relative to control condition | Investigated therapeutic strategy | Refs |
|---|---|---|---|---|---|---|---|
| ACAT | Prostate, pancreas | Lung, liver, spleen, pancreas, lymph node | Human PC-3M, PC-3, MIA PaCa-2 cells | Avasimibe | Reduced invasion and proliferation | Metastasis prevention | 137,138 |
| ALT2 | Breast | Lung | Murine 4T1 cells, human MCF7 cells | shRNA knockdown | Reduced tumour size | Metastasis prevention | 69,175 |
| ASCT2 | Prostate | Liver (trend), lung (significant effect) | Human PC-3 cells | shRNA knockdown | Reduced tumour growth | Metastasis prevention | 92 |
| ASNS | Breast | Lung | Murine 4T1-T cells | shRNA knockdown, asparaginase, low-asparagine diet, combination of shRNA and drug or diet | No significant change in response to single treatments | Metastasis prevention | 177 |
| CD36 | Head and neck, breast, skin | Lymph node, lung, liver, bone | Patient-derived SCC tumours, murine SCC Ln-7 cells, human MCF7 cells, human 501mel cells | shRNA knockdown, neutralizing antibodies FA6.152, JC63.1 | No changes or slight reduction (one shRNA) of tumour growth | Metastasis prevention and treatment | 103 |
| CPT1A | Colon and/or rectum | Lung, liver | Human HCT15, HCT116 | Etomoxir, shRNA knockdown | n.d. | Metastasis prevention | 185 |
| FABP4 | Ovaries | Diaphragm, liver, spleen, lymph node, pelvic areas, omentum | Human HeyA8 MDR, Ovcar 5, OVCAR8 cells, murine ID8 cells | DOPC nanoliposomes containing siRNA injections, CRISPR knockout, BMS309403 | No changes (BMS309403) or reduced tumour weight | Metastasis prevention and treatment | 118,156 |
| FABP5 | Cervix, prostate | Lung, femur, lymph node | Human SiHa cells, PC-3 | siRNA, shRNA knockdown | Reduced tumour size | Metastasis prevention | 122,124 |
| FASN | Ovarian, skin, colorectal | Peritoneum, lung, liver, lymph node | Human SKOV-3, KM-20, HT29 cells, murine B16-F10, | shRNA knockdown, orlistat | Reduced tumour growth | Metastasis prevention | 127,128,157 |
| GDH | Lung | Liver, lung | Human A549, H460 | shRNA knockdown | n.d. | Metastasis prevention | 91 |
| GLS1 | Colorectal | Lung, liver, kidney | Human HT29 cells, murine VM-M3 cells | shRNA knockdown, 6-diazo-5-oxo-l-norleucine (DON) | Decreased tumour volume and weight | Metastasis prevention | 80,93 |
| LDHA | Breast | Lung | Human MDA-MB-231 cells | shRNA knockdown | Reduced tumour growth | Metastasis prevention | 37,39 |
| MCT1 | Skin | Lung | Patient-derived xenografts, murine YUMM1.7, YUMM3.3, YUMM5.2 cells | shRNA knockdown, AZD3965 | No change (AZD3965) or slight (one shRNA) reduction of tumour size | Metastasis prevention | 63 |
| MCT2 | Breast | Lung | Murine 4T1, EMT6.5 cells | CRISPR knockout, α-cyano-4-hydroxycinnamic acid | No (volume) to slight (weight) effect on tumour growth | Metastasis prevention | 69 |
| P4HA | Breast | Lung, lymph node | Human MDA-MB-231, MDA-MB-435 cells | shRNA knockdown, ethyl 3,4- dihydroxybenzoate | Reduced tumour volume | Metastasis prevention | 70 |
| PC | Breast | Lung | Murine D2A1 cells | shRNA knockdown | No significant effect | Metastasis prevention | 68 |
| PHGDH | Breast, kidney | Lung, brain | Human MDA-MB-231, MDA-MB-231 BrM cells, patient-derived clear cell renal cell carcinoma cells | shRNA knockdown, PH-755 | Similar to increased tumour mass | Metastasis prevention and treatment | 173,174 |
| PRODH | Breast | Lung | Murine 4T1, EMT6.5 cells | l-THFA | No significant effect | Metastasis prevention | 73 |
| SCD1 | Skin | Lung | Murine B16-F10 cells, MITF+ B16-F1 | shRNA knockdown, CAY10566, A939572 | n.d. | Metastasis prevention but also promotion | 135,159 |
| xCT | Breast, oesophagus, gastrointestinal tract | Lung | Murine 4T1, TUBO cells, human KYSE-150 cells | Anti-xCT vaccination, sulfasalazine | Reduced tumour size | Metastasis prevention and treatment | 86,87,94 |
ACAT, cholesterol acyltransferase; ALT2, alanine aminotransferase 2; ASNS, asparagine synthetase; CPT1A, carnitine palmitoyltransferase 1A; FABP4, fatty acid binding protein 4; FASN, fatty acid synthase; GDH, glutamate dehydrogenase; GLS1, glutaminase 1; LDHA, lactate dehydrogenase A; MCT1, monocarboxylate transporter 1; n.d., not determined in the referenced metastasis study; P4HA, prolyl-4-hydroxylase; PC, pyruvate carboxylase; PHGDH, phosphoglycerate dehydrogenase; PRODH, proline dehydrogenase; SCC, squamous cell carcinoma; SCD1, stearoyl-CoA desaturase 1; shRNA, short hairpin RNA; siRNA, small interfering RNA; xCT, solute carrier family 7 member 11.