Table 2 Overview of agents targeting metabolic alteration by tumor suppressor genes
From: Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer
Tumor suppressor genes | Compound | Authors | Mechanisms | Clinical development | Cancer type/cell lines | Year of first publication |
|---|---|---|---|---|---|---|
TP53 | N-acetylcysteine (NAC) | Sablina et al. [97] | Preventing increased mutation rate and karyotype instability caused by p53 downregulation caused excessive oxidation of DNA | Experimental and/or preclinical | Lymphoma and Lung cancer | 2005 |
FX11 | Rajeshkumar et al. [26] | Inhibiting lactate dehydrogenase-A (LDH-A) which promote pyruvate to metabolize to lactate during the process of aerobic glycolysis | Experimental and/or preclinical | Pancreatic cancer | 2015 | |
APR-246 | Peng et al. [99] | Inhibits the oxidoreductase enzyme thioredoxin reductase 1 (TRXR1) and converts the enzyme to a pro-oxidant NADPH oxidase, thereby inducing oxidative stress | Experimental and/or preclinical | H1299-His175, Saos-2-His273 cells | 2013 | |
APR-246 | Liu et al [101] | Depleting glutathione (GSH) and thereby inducing lipid peroxidative cell death | Experimental and/or preclinical | Oesophageal cancer | 2017 | |
APR-246 | Ali et al. [102] | Increasing expression of genes that are related to oxidative stress including haeme oxygenase 1 (HMOX1) and so on | Experimental and/or preclinical | Acute myeloid leukaemia | 2016 | |
APR-246 | Lambert et al. [100] | Inducing endoplasmic reticulum stress by its redox effects | Experimental and/or preclinical | Saos-2 cells | 2010 | |
| Â | Pramlintide | Venkatanarayan et al. [98] | Inhibiting glycolysis and inducing reactive oxygen species (ROS) and apoptosis through calcitonin receptor (CalcR) and receptor activity modifying protein 3 (RAMP3) | Experimental and/or preclinical | thymic lymphoma | 2015 |
LKB1 | ND-646 | Svensson et al. [119] | Inhibiting Acetyl-CoA carboxylase (ACC), which is a product in the first step of fatty acid (FA) synthesis, thus inhibiting FA synthesis and tumor growth | Experimental and/or preclinical | Non-small-cell lung cancer | 2016 |
Adenoviruses expressing Cre and/or Flp recombinase | Kottakis et al. [117] | Induction of the serine-glycine-one-carbon pathway coupled to S-adenosylmethionine generation, and thus sensitizes cells and tumors to inhibition of serine biosynthesis | Experimental and/or preclinical | Pancreatic cancer | 2016 | |
Cb-839 | Galan-Cobo et al. [86] | Enhanced energetic/redox stress, tolerated through activation of KEAP1/NRF2- in a glutamine-dependent manner enhanced glutamine dependence and vulnerability to glutaminase inhibition | Experimental and/or preclinical | Non-small-cell lung cancer | 2019 | |
PTEN | Avasimibe | Li et al. [123] | ACAT inhibition increased intracellular free cholesterol level and caused elevated endoplasmic reticulum stress and apoptosis | Experimental and/or preclinical | Pancreatic cancer | 2016 |
Oroxylin A | Zhao et al. [103] | Inducing the downregulation of mouse double minute 2 (MDM2) transcription by promoting the lipid phosphatase activity of PTEN, and further suppress the MDM2-mediated degradation of p53, thereby inhibiting glycolysis | Experimental and/or preclinical | MCF-7 and HCT116 cells | 2015 |