New cancer drugs appear, Dawning researchers found new strategies for cancer treatment

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New cancer drugs appear, Dawning researchers found new strategies for cancer treatment

September 28, 2016 Source: Yao Dekang

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Researchers have found that small molecule drugs inhibit tumor cell fat synthesis and inhibit tumor growth in preclinical lung cancer models.

Recently, the Salk Institute for Biological Studies in San Diego, in collaboration with researchers at Nimbus Therapeutics in Boston, found that small molecule drugs inhibit tumor cell fat synthesis and inhibit tumor growth in preclinical lung cancer models. This represents a new strategy for treating cancer and is likely to be extended to treat other types of tumors, including liver cancer.

Lung cancer is one of the fastest growing morbidity and mortality rates in the world and one of the most threatening to human health. In order to enable rapid division and proliferation, tumor cells require a large amount of basic raw materials such as nucleic acids, proteins, and fats to construct cells. In order to be able to synthesize these basic raw materials in large quantities, tumor cells have modified their own metabolic systems. Targeting these engineered metabolic systems is becoming a new direction for researchers looking for cancer therapies. Many studies have focused on changes in the glucose and glutamine metabolic pathways in tumor cells, and in this study published in Nature Medicine, researchers have targeted their targets in fatty acid synthesis pathways in tumor cells.

Fatty acids are essential components of cell membranes and many organelles. One characteristic of tumor cells is the high rate of fatty acid synthesis. This means that if the rate of fatty acid synthesis can be suppressed, the growth of certain tumor cells can be inhibited. Researchers at the Salk Institute for Biological Research have found that the rate of fatty acid synthesis is controlled by Acetyl-CoA Carboxylase (ACC), and inhibition of ACC expression by antisense RNA leads to apoptosis of tumor cells. Researchers at Nimbus Therapeutics have successfully developed a small molecule inhibitor called ND-646 that effectively and specifically inhibits ACC activity through allosteric regulation.

The study found that ND-646 was able to reduce the size of non-small cell lung cancer tumors transplanted into mice by nearly two-thirds. At present, the standard drug carboplatin for the treatment of non-small cell lung cancer can only reduce the tumor volume by 50% under the same conditions. The combined use of carboplatin, which causes DNA damage, and ND-646, which inhibits fat synthesis, is particularly effective, reducing tumor volume by 87%! Even more surprisingly, the combination of carboplatin and ND-646 has a toxic side effect on normal cells. small.

“We found that some innovative ACC inhibitors have very good tolerance and bioavailability, which means they are not far from the standards that can enter clinical trials.” The first author of the article, Salk Bio Dr. Robert Svensson, research assistant at the institute, said.

"This is the first time someone has been able to show that ACC is needed for tumor growth, and there is convincing evidence that targeted lipid synthesis is a new way to fight cancer," added senior author of the article, Professor Reuben Shaw of the Salk Institute for Biological Research. Says: "We will add a new weapon to the arsenal of cancer."

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