Table 2.
Therapeutic perspectives in lipid metabolic pathways.
| Targets | Drug name | Type of cancer | Beneficial effects | Stage of development | References/clinical trial number |
|---|---|---|---|---|---|
| CD36 | CD36 monoclonal antibody | Prostate cancer | Reduced fatty acid uptake and the abundance of oncogenic signaling lipids | Preclinical | (99) |
| FASN | IPI-9119 | Castration-resistant prostate cancer | Selectively inhibit FASN and suppress expression of both full-length of androgen receptor (AR) and AR variant V7 | Preclinical | (23) |
| Orlistat | Prostate, breast, ovarian, colon cancer, and other solid tumors | An anti-obesity drug approved by FDA and an irreversible inhibitor of FASN | Preclinical | (100, 101) | |
| TVB-2640 | Solid Malignant Tumor | A potent and reversible FASN inhibitor | Phase 2 Phase 2 Phase 1 Phase 1 |
NCT03032484 NCT03179904 NCT02980029 NCT02223247 |
|
| TVB-3166; TVB-3664 |
Oral squamous cell carcinoma, colorectal, breast cancer | A reversible and selective FASN inhibitor | Preclinical | (102, 103) | |
| Conjugated Linoleic Acid | Breast Cancer | Reduce FASN gene expression and spot 14 | Early Phase 1 | NCT00908791 | |
| Omeprazole | Triple negative breast cancer | A proton pump inhibitors that can inhibit FASN | Phase 2 | NCT02595372 | |
| ACC | TOFA | Lung cancer and colon carcinoma | Induce apoptosis as an allosteric inhibitor of ACC-alpha | Preclinical | (104) |
| Soraphen A | Prostate cancer | Inhibit fatty acid synthesis and stimulate fatty acid oxidation | Preclinical | (105) | |
| ND-646 | NSCLC | Inhibit fatty acid synthesis and tumor growth as an allosteric inhibitor of the ACC | Preclinical | (106) | |
| mTOR | Rapamycin (<x>RAD001</x>) |
Breast cancer | Inhibit S6 phosphorylation and cell proliferation, and resulted in lower levels of apoptosis induction | Preclinical | (107, 108) |
| Everolimus | Castrated Resistant Prostate Cancer; Locally Advanced Cervical Cancer | Directly inhibit mTORC1 and indirectly inhibit mTORC2 | Phase 3 Phase 1 |
NCT03580239 NCT01217177 |
|
| PF-05212384 | Advanced Cancer; Advanced squamous cell lung, pancreatic, head and neck, and other solid tumors |
Intravenous PI3K/mTOR inhibitor | Phase 1 Phase 1 |
NCT01347866 NCT03065062 |
|
| PF-04691502 | Breast Neoplasms | Inhibit PI3K and mTOR kinase | Phase 2 | NCT01658176 | |
| Vistusertib/AZD2014 | Endometrial, triple negative breast cancer, ovarian, primary peritoneal, or fallopian tube cancer | mTORC1/2 Inhibitor | phase 1b/2 | NCT02208375 | |
| AKT | MK-2206 | Advanced or metastatic solid tumors or breast cancer; prostate cancer | Inhibit Akt phosphorylation, cell proliferation and apoptosis in a dose-dependent manner | Phase 1 Phase 2 Phase 2 |
NCT01245205 NCT01277757 NCT01251861 |
| Capivasertib/ AZD5363 |
Breast cancer, prostate cancer, and advanced solid tumors | A novel pan-AKT kinase catalytic inhibitor | Phase 1 Phase 1 Phase 2 Phase 1/2 |
NCT03310541 NCT01226316 NCT02525068 NCT01992952 |
|
| GSK2141795 | Endometrial cancer | AKT inhibitor | Phase 1 | NCT01935973 | |
| SREBP | Betulin | BRAFV600E-mutant melanoma | Increase membrane lipid poly-unsaturation and lipid peroxidation; sensitize therapy-resistant melanoma cells to MAPK-targeting therapy | Preclinical | (26) |
| Fatostatin | Prostate cancer | A non-sterol diarylthiazole derivative which has antimitotic properties and perturbs nuclear translocation of SREBP and androgen receptor signaling | Preclinical | (109) | |
| PF-429242 | HCC | A reversible site 1 protease inhibitors, which inhibits endogenous SREBP processing | Preclinical | (110) | |
| AMPK | 5-aminoimidazole 4-carboxamide riboside (AICAR) | Prostate cancer | An AMPK activator which inhibits cell growth | Preclinical | (111) |
| SCD1 | A939572 | Glioblastoma and renal cell carcinoma | Inhibit tumor growth both in vitro and in vivo; overcoming chemotherapy agent resistance | Preclinical | (112, 113) |
| CVT-11127 or CVT-12012 | Lung cancer | A small molecule SCD inhibitor which modulate cancer cell metabolism, proliferation and survival | Preclinical | (114) | |
| MF-438 | Lung cancer | Induce lung cancer stem cells apoptosis | Preclinical | (115) | |
| CPT1 | Etomoxir | Glioma | A CPT1 inhibitor which inhibits proliferative activity | Preclinical | (41) |
| Perhexiline | Breast and gastrointestinal cancer | A CPT1 inhibitor which blocks FFA utilization, OxPhos, and proliferation | Preclinical | (116, 117) | |
| MAGL | Three different types of MAGL inhibitors | — | Potent and reversible MAGL inhibitors | Preclinical | (118–120) |
| HMGCR | Statin, e.g., lovastatin, atorvastatin, rosuvastatin and simvastatin | Various leukemia and solid tumors | Inhibitors of HMGCR | Phase 2 Phase 2 Phase 2 Phase 2 |
NCT03358017 NCT03324425 NCT02569645 NCT03275376 |
| LXR | GW3965; LXR623 | Melanoma and glioblastoma | LXR agonists which suppress mitochondrial respiration and decrease cholesterol levels by enhancing the excretion and decreasing the resorption of cholesterol | Preclinical | (121) |
| ApoA-I | ApoA-I mimetic peptides | — | Mimetic peptides which is synthesized on the basis of α-amphipathic helical repeating structure of ApoA-I | Preclinical | (78) |
| Apabetalone (RVX-208) | Colorectal cancer | A BET inhibitor which is a stimulator of ApoA-I and regulate the reverse cholesterol transport | Preclinical | (77) | |
| ACAT | K604 | Glioblastoma | A selective ACAT1 inhibitor, which suppresses proliferation of glioblastoma cells | Preclinical | (122) |
| ATR-101 | Advanced adrenocortical carcinoma | An oral selective ACAT inhibitor | Phase 1 |
NCT01898715 (123) |