New molecular clues shed light on how endometrial cancer develops.

Recently, the results of a very innovative investigation in relation to the molecular steps that occur to develop endometrial cancer have been published in the scientific journal “Cell”. The study provides very important information in order to more precisely identify which patients will really need more aggressive treatment.
It is a collaborative study between more than 10 scientific institutions and funded by the National Cancer Institutes of the United States that, in addition, opens the door to new molecular drugs already approved for other diseases and that could now be investigated in endometrial cancer.
Although the study shows detailed molecular information on endometrial cancer, the information is so extensive that it must be interpreted little by little. This is because it shows the action of multiple molecules in different pathways of intracellular molecular action.
“This is like the Google Earth of endometrial cancer, according to Karin Rodland, a biologist at the US Department of Energy’s Pacific Northwest National Laboratory and one of the five authors of the publication.
95 different uterine tumors were analyzed along with 49 normal uterine tissue samples. The scientists determined more than 12 million measurements, including genes, messenger RNA, circulating blood RNA, microRNAs and proteins.
The researchers created a novel way to identify certain endometrial tumors traditionally classified as non-aggressive but actually more aggressive. For example, a protein (beta-catenin) was found to interact with a signaling pathway to accumulate and stimulate cells to grow uncontrollably.
In addition, the team of scientists developed a new way to determine which patients are most likely to benefit from certain specific molecular treatments (pembrolizumab, nivolumab), which bypass the barriers used by some tumor cells to evade the immune system. This represents yet another example to explore the use of immunotherapy to stimulate the body’s natural defenses to fight cancer.
The study proposes a new measure focused on the patient’s antigen presentation machinery, known as APM.
In short, a better understanding of who will benefit from the different molecular drugs will make it possible to avoid their unnecessary use, with the consequent reduction in unjustified adverse effects. “This work contributes to the personalized medicine we need to provide to patients who have endometrial cancer,” said Bing Zhang of Baylor College of Medicine. Such work will help us learn which patients will benefit most from which therapies.”

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