Mapping tumors and genetic changes within them could help develop new cancer treatments
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We now have some of the most detailed maps ever created for some cancers, as well as new tools and methods to analyze them. The findings come from a cancer mapping effort called the Human Tumor Atlas Network, which provides clues about how cancers form, evolve and become resistant to treatments. I will.
Cancer occurs when genetic mutations cause cells to grow and multiply out of control. Much of what we know about this disease comes from genetic analysis of tumors. Until recently, this could only be done by combining and analyzing all the genetic data within a tumor sample at once, making it impossible to identify individual cell types.
However, tumors are not monolithic. “They are complex ecosystems made up of not just tumor cells but also immune cells, endothelial cells, and other supporting cells,” said Daniel Abravanel of the Dana-Farber Cancer Institute in Boston. say.
Thanks to the advent of more sophisticated tools, teams of researchers are now able to identify individual cells from nearly 2,000 people with 20 different cancer types and determine their function within tumors. Now you can.
As part of the study, Li Ding and colleagues at Washington University in St. Louis, Missouri, mapped 131 tumor regions in 78 people with cancer types that appear in the breast, colon, pancreas, kidney, uterus, and bile ducts. did. Connects the liver and gallbladder to the small intestine. They used a technique called single-cell sequencing to measure which genes were turned on or off in each cell of the tumor sample.
The researchers also viewed the tissue samples under a powerful microscope to determine the location and structure of the cells. They then built a 3D model of the tumor to show how the cells within the tumor are organized and interact. They found that within tumors, cancer cells form distinct clusters known as microregions. The researchers then grouped these regions based on similar genetic changes, such as high or low immune cell activity. Evolution in the genetic activity of cells within microregions is thought to be a major factor in why cancers become resistant to treatment.
Further research from the Human Tumor Atlas Network suggests that multiple cells may work together to form colon cancer. “For decades, the consensus in the field was that tumors arise from single cells,” says Doug Winton of the University of Cambridge.
Winton and his colleagues used genetically engineered mice whose cells changed color when they developed cancer. This made it possible to identify and track tumors as they form in the intestines of animals. Researchers found that about 40 percent of colon tumors originate from multiple cells that work together to outcompete neighboring cells.
Another group of researchers, led by Ken Lau at Vanderbilt University in Tennessee, has also identified biomarkers for monitoring tumor evolution. Because naturally occurring mutations cause permanent genetic changes in tissues, the researchers were able to reconstruct the sequence of events and create a molecular timeline of each tumor’s growth.
Using this approach, they analyzed early progenitor cells of mouse and human colon cancers and found that up to 30 percent were of multicellular origin. Currently, the best predictor of whether a precancerous lesion in the colon will turn into cancer is its size, Lau said. Understanding how colon cancer forms will improve our ability to screen for precancerous lesions and detect cancer early, he says.
Cancer mapping projects have revealed some surprising things. Abravanel and his colleagues took 67 tumor biopsies from 60 patients with metastatic breast cancer, meaning the cancer had spread to other organs such as the liver, brain, or lungs. They found that samples collected from the same participants at different time points were genetically very similar. “You would expect different mutations to evolve over time,” Abravanel says.
As part of the project, researchers led by Princeton University’s Ben Rafael developed an algorithm to quantify the proportion of cancerous and non-cancer cells in tumors and explore how these cells interact. Created. This can also help identify how the tumor is growing.
These discoveries bring us one step closer to understanding how cancer forms and evolves, which may in turn lead to improved treatments. Abravanel says this could also be useful in his clinical practice. “While we do the best we can to match the right treatment to the right patient, we are rarely able to derive the best treatment for each individual case.” in the moment. ”
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