We now have some of the most detailed maps ever made of various types of cancer and new tools and methods to analyze them. The findings come from an initiative to map cancers. Human Tumor Atlas NetworkIt provides clues about how cancers form, develop, and become resistant to treatment.

Cancer develops when genetic mutations encourage cells to grow and multiply uncontrollably. Most of what we know about the disease comes from genetic analysis of tumors. Until recently, we could only do this by combining and analyzing all the genetic data from a tumor sample at once; this made it impossible to identify individual cell types.

However, tumors are not monolithic. “These are complex ecosystems that include not only tumor cells but also immune cells, endothelial cells and other supporting cells,” he says. Daniel Abravanel at the Dana-Farber Cancer Institute in Boston.

Thanks to the advent of more sophisticated tools, a research team can now identify individual cells or determine their functions in tumors from nearly 2,000 people with 20 different types of cancer.

As part of the study, Li Ding Colleagues from Washington University in St. Louis, Missouri, mapped 131 tumor sites from 78 people with types of cancer that occur in the breasts, colon, pancreas, kidneys, uterus, and bile ducts that connect the gallbladder to the liver. small intestine. They used a technique called single-cell sequencing to measure which genes were turned on and off in each cell of a tumor sample.

The researchers also examined tissue samples under powerful microscopes to determine the location and structure of the cells. They then created 3D models of the tumors; They showed how cells in these models are organized and interact. They found that inside tumors, cancer cells form distinct clusters known as microdomains. The researchers then grouped these areas according to similar genetic changes, such as high or low immune cell activity. Evolution in the genetic activity of cells within microdomains appears to be an important factor in cancers becoming resistant to treatment.

Further research from the Human Tumor Atlas Network suggests that multiple cells can sometimes coordinate to form colon cancer. “For decades, the consensus in the field was that tumors arise from a single cell,” he says. Doug Winton at Cambridge University.

Winton and his colleagues used genetically modified mice to make their cells change color when they developed cancer. This made it possible to identify and track tumors that formed in the animals’ intestines. Researchers found that approximately 40 percent of colon tumors arise from multiple cells cooperating to outcompete neighboring cells.

A separate group of researchers led by Ken Lau at Vanderbilt University in Tennessee identified biomarkers to monitor tumor development. Naturally occurring mutations create permanent genetic changes in tissue; This allows researchers to reconstruct the sequence of events and create a molecular timeline of each tumor’s growth.

Using this approach, they analyzed early precursors of colon cancer in mice and humans and found that up to 30 percent had a multicellular origin. The best predictor we currently have for determining whether a precancerous lesion in the colon will become cancerous is its size, Lau says. Understanding how colon cancer occurs could improve our ability to screen for precancerous lesions and detect cancer earlier, he says.

The cancer mapping project revealed some surprises. Abravanel and colleagues collected 67 tumor biopsies from 60 people. metastatic breast cancerThat is, it had spread to other organs such as the liver, brain and lungs. They found that samples collected from the same participant at different time points were genetically very similar. “You would expect to see different mutations evolve over time,” says Abravanel.

Within the scope of the project, under the leadership of researchers I am Raphael at Princeton University I created an algorithm This method, which measures the ratio of cancerous and non-cancerous cells in a tumor and investigates how these cells interact, can also help understand how the tumor grows.

Together, these discoveries bring us one step closer to understanding how cancer forms and develops, which could improve treatment. Abravanel says this can also be helpful in clinical practice: “We try our best to match the right treatment to the right patient, but for individual cases we are largely unable to uncover what the best treatment will be at that exact moment.”