How cell atlases and 3D mapping will change prevention and therapy

In a set of 12 studies published in the journal NatureResearchers at the Human Tumor Atlases Network (HTAN) have analyzed hundreds of thousands of cells from human and animal tissues, leading some studies to produce 3D maps of tumor cells, known as cell atlases, and others to develop “clocks.” molecular tests” to track cellular changes that lead to cancer.

These detailed maps, showing the position of cells in tumors and studying their biology, reveal key information. on the development of various types of cancerincluding breast, colon and pancreas, and may offer clues to new treatments. In some of these studies, researchers created cell atlases that made it possible to analyze tumors at single-cell resolution and study the onset of cancer. The team examined cellular organization in 131 samples of six types of cancer, including breast, colon, pancreatic and kidney cancer. The results showed that different areas of the same tumor may respond differently to drugs. This knowledge of how different groups of cancer cells respond to treatment could help develop more effective treatments.

Other studies used 3D mapping to analyze samples of colon polyps—abnormal growths of the intestinal lining that can develop into cancer. The researchers identified molecular changes in the cells of these polyps, such as loss of DNA bonds and modifications in gene activity. They also observed changes in the immune response, cell growth and hormonal metabolism that occur early and may predispose polyp cells to cancer.

Therapy targeting these changes may improve cancer treatment and early interventionbecause experts agree that the best treatment for cancer is prevention. “If we can understand how different populations of cells respond to environment and diet, how these factors influence tumor occurrence, and how different lineages of cells contribute to this process, we can develop better methods of prevention and early detection,” Omer said. Yilmaz, a stem cell biologist at the Massachusetts Institute of Technology in Cambridge.

More complex tumors

Other atlases provide insight into why some types of cancer are more difficult to treat. “Tumors are made up of more than just cancer cells,” explained Daniel Abravanel, a physician-scientist at the Dana-Farber Cancer Institute in Boston and co-author of the breast cancer study. This showed that immunotherapy, which does not act directly on cancer cells but rather aims to strengthen the immune system to eliminate them, shows less effectiveness in breast cancer compared to other types.

To analyze this difference, the researchers created a 3D tumor atlas from dozens of samples from 60 patients with aggressive forms of breast cancer. They examined the distribution of immune cells and found that Certain types of these cells were more common in some tumors.especially in patients receiving immunotherapy. In three cases, biopsies of the same tumor 70 to 220 days apart revealed differences in levels of immune cells, particularly T cells and macrophages. In two of these cases, the number of these cells decreased over time, while in the third there was an increase.

In another study, they found that some aggressive subtypes of breast cancer contain more immune cells than others, which wear out over time. These cells expressed CTLA4 proteinwhich limits its ability to respond to tumors. Therapy targeting CTLA4 has shown promising results in the treatment of melanoma and lung cancer.

molecular clock

Other advances in the field have shown how cells become cancerous in the first place. In colorectal cancer research, they developed a “molecular clock” to track the process by which normal cells begin to become “rogue” and multiply uncontrollably in the intestines. They used single-cell analysis along with the gene-editing tool CRISPR to introduce mutations into the DNA of each cell. The idea was that these mutations functioned as time markers, recording the chronology of each cell’s changes and divisions.

The team applied this approach to 418 human colon polyps and found that up to 30% of these polyps originate from multiple cell types rather than from a single cell. In 60% of cases, one group of cells, as the polyp grew, began to “overtake” others, turning into a tumor. Likewise, two similar studies in mice, which included analysis of 260,922 individual cells from 112 intestinal tissue samples, confirmed that a mixture of cells collectively initiates colorectal tumors.

These findings challenge previous beliefs that colon cancer arises solely from individual rogue cells in the intestinal lining. Instead they assume that Cellular complexity plays a critical role in tumor developmentwhich may open up new opportunities for diagnosis and early intervention in this disease.

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