Cancer cells possess unique metabolic properties that allow rapid proliferation even in low oxygen and nutrient conditions. Researchers have discovered that targeting these altered metabolic pathways in cancer cells can potentially halt tumor growth. Several biotech companies are developing new drugs that interfere with cancer metabolism based therapeutics to achieve cell death or regression.
One major difference in cancer cell metabolism is increased glycolysis even under normal oxygen levels, termed as Warburg effect. Researchers at MetaboloThera are developing inhibitors against key glycolytic enzymes that are overexpressed in cancers like lactate dehydrogenase and pyruvate kinase M2. Their lead compound MT-7 has shown promise in preclinical models by blocking glycolysis and inducing apoptosis in tumor cells. The company aims to start phase 1 clinical trials by early 2023 once IND enabling studies are complete.
Another metabolic alteration seen in cancers is increased glutaminolysis due to high glutamine consumption. Abraxis BioScience has created ABX-GLN1, a small molecule inhibitor of glutaminase C which breaks down glutamine to feed the tricarboxylic acid (TCA) cycle. In animal studies, ABX-GLN1 was found to reduce tumor growth and viability by depleting glutamine levels inside cancer cells. Abraxis plans to file an IND for phase 1 studies before the end of 2022.
Targeting Lipid Metabolism In Cancer Metabolism Based Therapeutics
Rapidly proliferating cancer cells need lipids and cholesterol for producing new Cancer Metabolism Based Therapeutics. Several pharmaceutical firms are testing inhibitors of key enzymes involved in lipid biosynthesis.
Acetyl CoA carboxylase (ACC) catalyzes the first committed step in fatty acid synthesis which is overexpressed in certain cancers. MirZen Therapeutics developed a potent ACC inhibitor MZ3 that showed robust anti-tumor efficacy against xenograft models of breast and lung cancer. It is undergoing toxicology studies before initiating an early phase clinical trials program.
Cholesterol is an important component of cell membranes and its homeostasis is dysregulated in cancer. Nexus Pharma has created an inhibitor named NP-5 targeting squalene synthase which is essential for cholesterol biosynthesis from farnesyl pyrophosphate. In preclinical models, NP-5 significantly reduced tumor growth and increased apoptosis in hepatocellular carcinoma and glioblastoma cells by depleting cellular cholesterol levels. The compound entered phase 1 trials earlier this year.
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