This article is from WeChat public account:Academic latitude (ID: Global_Academia), title map from: Visual China
Some people say that cancer cells are like greedy vampires, constantly vying for nutrition in the human body to promote their growth. It is also conceived that if you can block the mouth of cancer cells, can you starve cancer cells and treat cancer? In today’s “Science” paper, we see the gratifying results of this idea in animal models.
Physically, cancer cells need an amino acid called glutamine, which plays an important role in the synthesis of DNA, proteins, and lipids. As early as the 1950s, scientists developed a drug called DON that effectively inhibits the use of glutamine-enzymes, making it impossible for cancer cells to “eat” glutamine. In this way, cancer cells will be “starved.”
However, a series of clinical trials have shown that the drug has enormous toxic side effects. This is also understandable. Cancer cells require glutamine, which is also needed for normal cells. Put DON directly into the body, then it must not affect normal cells?
To this end, the research team changed its mind. They use the “prodrug” of DON. What does this mean? That is to say, the “prodrug” will become DON only after additional metabolism. Under normal circumstances, this “prodrug molecule” will circulate in the blood without playingeffect. However, in the tumor microenvironment, the structure of this molecule changes to become DON that inhibits glutamine absorption. In this way, we can control the effect of the drug only in the vicinity of the tumor.
“Most active drugs will be in the position we want them to arrive,” said Professor Jonathan Powell, co-author of the study.
This drug (red) reduces tumor volume and prolongs mouse survival in a variety of tumor models (Source: References [1] ])
Imagine that this “prodrug molecule” can really exert anti-cancer effects in animals without causing serious side effects? To answer this question, scientists used a variety of different mouse cancer models, which were injected with colorectal cancer, lymphoma, and melanoma.
The results of the study showed that under the treatment of this drug, the tumor volume was significantly reduced, and the survival of mice was also prolonged. In contrast, the tumor volume of the control group was up to 5 times that of the treatment group.
What’s even more gratifying is that follow-up studies have shown that the treatment group achieved such good results, on the one hand, by inhibiting the absorption of glutamine by cancer cells, and on the other hand because immune T cells are not affected. The impact of this drug.
This is not to say that this drug molecule does not work for T cells. On the contrary, it can also inhibit the absorption of glutamine by T cells. But T cells have multiple biochemical pathways that can be used, one is inhibited, and another can be used to synthesize key molecules such as DNA, while cancer cells do not. The researchers pointed out in a news report in Science today that this drug can inhibit the proliferation of tumors and prevent it from escaping the immune system.
Other scientists have also highly rated this research. Some scientists point out that this is the first study to show that T cells and cancer cells have different responses to glutamine inhibition. Others believe that the drug “miraculously” does not affect T cells and is expected to become a novel cancer therapy.
But we also need to note that many drugs that have magical effects on mice do not necessarily work in human patients. Therefore, we also need human clinical trials to assess the anticancer potential of this molecule. The good news is that next year scientists plan to launch a phase 1 clinical trial to assess the safety of the therapy. We look forward to hearing more good news.
References:
[1] Robert D. Leone et al., (2019), Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion, Science, DOI: 10.1126/science.aav2588< /span>
[2] Revamped cancer drug starves tumors in mice, Retrieved November 7, 2019, from https://www.sciencemag.org/news/2019/11/revamped-cancer -drug-starves-tumors-mice
This article is from WeChat public account:Academic latitude (ID: Global_Academia) , title map from: Visual China