RNA sequencing has shown a previously unknown dimension to the way malignant cells work—which could lead to novel treatments

from Scientfic American by Philip Ball 

When Brad Bernstein first looked at cancer tumors cell by cell in 2014, what he found dismayed him: he realized that in any single tumor, there is not one type of cancer cell at work but many. “I was a little depressed when I saw it,” says Bernstein, a pathologist at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. “Some of the toughest tumors out there are really heterogeneous mixtures [of cells].”

But for many clinicians and surgeons working to treat cancer, this observation about the nature of tumor cells was a glass more half-full than half-empty. They already knew that treating some tumors is an incredibly difficult problem, Bernstein says, “and now you’ve shed light on why it’s an incredibly difficult problem.”

In order to zoom in and look at a tumor one cell at a time, Bernstein and his colleagues use a technique called single-cell RNA sequencing (scRNA seq). It shows, in principle, what each individual cell in a sample is doing and which genes within that cell are active. This technology is revealing a whole new dimension to cancerous tumors—that they are mosaics of different cell types, more like loosely structured organs than an undisciplined mass of replicating cells, as was previously thought. And these tumor cells can change their developmental path in a fluid manner, presenting unique challenges—and opportunities—for treatment.

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