TABLE 1.
Key enzymes in the acetyl-CoA metabolic pathway with a profound impact on cancers.
| Enzyme | Cancer type | Effect | Methods references |
|---|---|---|---|
| ACC | Lung cancer, colorectal cancer, colon adenocarcinoma, etc. pancreatic cancer | Spiropentacylamide derivatives as ACC inhibitors may suppress tumor growth through increasing mitochondrial oxidation rates | Cell (Wei et al., 2018) culture |
| By using an ACC inhibitor (BAY ACC002), the proliferation of pancreatic cancer cells is slowed in vivo and in vitro, and the growth of pancreatic cancer is suppressed | Cell culture, (Petrova et al., 2017) animal models | ||
| ACSS2 | Breast cancer | An increased number of ACSS2 copies is associated with cancer progression and VY-3-135, an inhibitor of ACSS2, can inhibit tumor growth at a relatively low concentration | Cell culture, (Schug et al., 2015; Miller et al., 2021) animal models |
| Glioblastoma | Phosphorylation of ACSS2 on serine 267 stabilizes ACSS2 protein levels and contributes to glioblastoma growth | Cell culture (Ciraku et al., 2022) | |
| Pancreatic cancer | ACSS2 knockout markedly inhibits cancer cells proliferation and the prolongation of survival in orthotopic mouse models | Cell culture, (Zhou et al., 2022) animal models | |
| FASN | Breast cancer | Fasnall, a FASN inhibitor, has shown potential anticancer activity through the induction of apoptosis, especially when combined with carboplatin | Cell culture, (Alwarawrah et al., 2016) animal models |
| NSCLC, ovarian cancer, and breast cancer | For multiple cancers, the disease control rate based on a single FASN inhibitor administered alone reached 42%, and in trials of a FASN inhibitor used in combination with paclitaxel, the rate reached 70% | Clinical (Falchook et al., 2021) studies | |
| Hepatocellular carcinoma | Stabilization of FASN through the ACAT1-GNPAT-FASN axis greatly contributes to the development of hepatocellular carcinoma | Cell culture, (Gu et al., 2020) animal models | |
| GLUD1 | Lung cancer, breast cancer, and leukemia | Targeting GLUD1 with the inhibitor r162 led to imbalanced redox and cancer cell proliferation | Cell culture, (Jin et al., 2015) animal models |
| Glioblastoma | Under hypoglycemic conditions, GLUD1 upregulates glucose transporters and promotes glucose uptake and cancer formation | Cell culture, (Wang et al., 2019b) animal models and clinical studies | |
| Kidney renal clear cell carcinoma (KIRC) | GLUD1 is degraded following amino acid deprivation, thus inhibiting RP gene expression and retaining nutrition to maintain cancer cells growth | Cell culture, (Shao et al., 2021) animal models |