Reviewed by James Ives, M.Psych. (Editor) Feb 14 2020
A study published Feb. 13 in Cell provides an unprecedented look at the dozens of molecular steps that occur to bring about endometrial cancer, commonly known as uterine cancer. The study offers insights about how physicians might be able to better identify which patients will need aggressive treatment and which won't, and offers clues about why a common treatment is not effective with some patients.
The study, funded by the National Cancer Institute, also suggests a potential new role for already-approved drugs that target proteins known as CDK12, SMARCA4 and PML in other types of cancer.
One could say that the work is a detailed molecular snapshot of endometrial cancer. However, the information is so vast, touching upon tens of thousands of molecular actors taking part in thousands of interactions at different times, that the work is more like a frame-by-frame video, documenting steps that play out over years in patients' bodies.
This is like the Google Earth of endometrial cancer. It's a very comprehensive portrait of this particular cancer type. We tried to measure everything we possibly could. Then we searched for patterns." Karin Rodland, one of five corresponding authors of the paper and cancer biologist at the U.S. Department of Energy's Pacific Northwest National Laboratory
Rodland and PNNL's Tao Liu are two of five corresponding authors of the paper; the others come from New York University School of Medicine, Washington University in St. Louis, and Baylor College of Medicine. Overall, scientists from more than a dozen institutions contributed. The senior author is David Fenyo of NYU Langone Health. Endometrial cancer: beyond genes
The research builds on work by The Cancer Gene Atlas, or TCGA, which identified some of the genetic underpinnings of the disease in 2013.
But genes are only the start of the story when it comes to cancer. When and where are those genes turned on, turned off, or mutated? What do they produce and how do those products interact?
The team studied 95 uterine tumors and 49 normal uterine tissue samples. Scientists measured the abundance and modifications of a dizzying array of molecular players, including genes, messenger RNAs, circular RNAs, micro RNAs and proteins. The measurements of what scientists call "post-translational modifications," including phosphorylation and acetylation , are key to determining when and where proteins, the molecular workhorses of every cell, are active or inactive.
"This unique, rich resource of high-quality data about all these molecular players from the same set of samples provides cancer researchers with a precious view of protein activity and regulation," said Liu.
Altogether the team took more than 12 million measurements.
What did they learn from the painstaking process? Here are the top takeaways. Identifying the most aggressive endometrial cancers
Scientists developed a promising new way to identify tumors that are not currently classified as aggressive but which turn out to be just as invasive as serous tumors, which grow quickly and are more likely than other tumors to kill patients.
Right now the aggressiveness of an endometrial tumor is determined largely by viewing the cells under a microscope. The team showed that activity levels of certain proteins clearly differentiate more-aggressive from less-aggressive tumors. For example, the team showed how the protein beta-catenin, a well-known actor in many types of cancer, interacts with a signaling pathway known as Wnt to evade detection, accumulate and spur cells to grow out of control. Related Stories
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