A research team led by scientists from Harvard University and Massachusetts Institute of Technology compared the way hematopoietic stem cells and leukemia cells consume nutrients in a new study, and found that cancer cells cannot tolerate their energy compared to normal cells. The supply has changed. These results suggest that there may be some methods that can target leukemia metabolism to promote cancer cell death without damaging other cell types. The researchers published their work in the journal Cell.
Dr. David Scadden, a professor of medicine at Harvard University, the senior author of the paper, said: “As early as decades ago, people knew that cancer cells use energy differently from most cell types. So we thought, maybe hematopoietic stem cells and their There may be some metabolic differences between direct offspring; are they so different from cancer that you can use something to manipulate energy to only affect cancer and not damage normal cells?"
Scadden's research team initially tested hematopoietic stem cells and their direct descendants, hematopoietic progenitor cells, which have relatively limited differentiation capabilities. The researchers changed the way cells take in nutrients in two ways: one is through the glucose on-off switch, and the other is like rotating a volume dial, which raises or lowers glucose through fine adjustments. Researchers found that turning off the glucose switch can lead to the death of stem cells, and increasing the glucose capacity dial can affect the normal energy production of offspring cells, making it better in some ways.
Scadden said: "This is an interesting difference between the two cell types. They have very different functions, and you can imagine that they will use their nutrients in very different ways, and no one has elucidated it before. "
The researchers then introduced some genes that were destroyed and could cause the parental hematopoietic stem cells and their progeny cells to become cancerous, allowing cancer cells to undergo the same glucose treatment as normal cells. The research team found that no matter which cell they started with, leukemia cells were sensitive to glucose on-off switches and volume dials.
Ying-Hua Wang (transliteration), the first author of the paper and a postdoctoral fellow in Scadden’s laboratory, said: “Some drugs are effective in killing cancer cells while also toxic to healthy cells. This is one of the main obstacles to cancer treatment. In this study In this article, we found a way to distinguish the sensitivity between normal cells and malignant cells, and proposed a potential therapeutic view."
Scadden said: "Cancer cells are not like normal cells in many ways. One of them is that cancer cells are locked in a specific behavior. The way these cells process glucose is so peculiar, they create a unique opportunity for intervention. . Normal cells will not be destroyed because they appropriately possess other energy mechanisms."
Some private companies have been developing drugs that target cancer metabolism, but they mainly target solid tumors. Scadden hopes that this research will open the door to industrial partners and generate some new therapies. More research is needed in the future to determine whether non-hematological cancers have similar differences in metabolic sensitivity.