In the past few years, new concepts from stem cell biology have transformed cancer research. Now, scientists recognize that many cancers are caused by inferior stem cells or progenitor cells. Traditional cancer therapies cannot effectively target and destroy the cancer-causing stem cells located in the center of the tumor, so they often cannot prevent the disease from recurring, as is the case with gliomas. The root cause of cancer is glial progenitor cells in the brain. These progenitor cells originate from stem cells and maintain the characteristics of stem cells, making up 3% of the cell population in the human brain. When the molecular machinery of glial progenitor cells goes wrong, these cells become cancerous and turn into glioma stem cells, leading to uncontrolled cell growth.
Goldman and his research team have long been engaged in the research of normal glial progenitor cells. These cells can produce astrocytes and oligodendrocytes. The former supports the function of neurons, and the latter produces myelin, ensuring long-distance conduction of nerve impulses.
The main research direction of the Goldman research team is to focus on the use of glial progenitor cells to treat neurological disorders such as multiple sclerosis, understand the biology of these cells, master the techniques of classification, identification and isolation of these cells, and then explore the causes that lead to these The molecular and genetic changes of cells to cancer.
Using human tissue samples representing the three main stages of glioma, the researchers identified and isolated carcinogenic stem cells. The lead authors of the paper, Dr. Romane Auvergne, Dr. Fraser Sim, and Goldman, then compared the gene expression profiles of these cancer stem cells with normal glial progenitor cells. Its purpose is to accurately describe the earliest genetic changes associated with cancer formation, to identify unique genes for cancer stem cells, and genes expressed at each stage of the disease process.
Among the 44,000 detected genes and sequences, scientists discovered a small group of genes that are overexpressed in all malignant stages of cancerous glial progenitor cells. These genes constitute a unique "tag" for identifying tumor progenitor cells, and scientists have also identified a set of corresponding potential therapeutic targets that exist in all stages of cancer.
"Finding an overexpressed protein or gene is an important thing you have to do in the development of cancer drugs. From this you can try to obtain therapeutic benefits by suppressing it," Goldman said.
The researchers tested this hypothesis by selectively targeting a gene called SIX1. SIX1 is highly expressed in glioma progenitor cells. Although this specific gene is actively expressed early in the development of the nervous system, it has not previously been observed in normal adult brains. People have always linked the SIX1 signal to breast and ovarian cancer, and people have raised the possibility of causing brain cancer. The result table clearly shows this. When the researchers blocked the expression of the disease, the tumor cells stopped growing and the implanted tumor shrank.
Goldman said: "This research provides us with a blueprint for developing new therapies. Now we can design a strategy to systematically analyze and eliminate compounds that have the potential to selectively target glioma stem and progenitor cells. These cells. By targeting genes such as SIX1 that are expressed in all stages of the glioma process, we hope to be able to effectively treat gliomas regardless of their malignant stage. Especially by targeting gliomas Starting cells, we hope that no matter where we start treatment, we can reduce the possibility of tumor recurrence. "
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