MADRID, 20 Abr. (EUROPA PRESS) –
A mutated gene found in more than 20 percent to 30 percent of breast cancer recurrences may help tumors become more aggressive and promote metastasis, a pair of new studies in carried out by researchers at the University of Pittsburgh (United States).
“We are excited about this research because it addresses an important clinical problem: a large number of deaths in breast cancer patients are the result of mutations in estrogen receptor genes. Our study provides a deeper understanding of how these mutations contribute to disease progression and also identifies potential vulnerabilities, which we hope will lead to the development of personalized treatment approaches.”
And it is that, about two thirds of breast tumors express estrogen receptor genes. Hormonal therapy can be very effective for these estrogen receptor-positive (ER+) tumors, but in about one-third of cases, the receptor mutates and no longer responds to this treatment.
As a first step toward developing new therapies for these patients, the multi-institutional team took a closer look at tumors harboring the ESR1 estrogen receptor gene with a mutation in one of several “hot spots” in the genetic code. Thus, they showed that these critical point mutations not only generate resistance to hormone therapy, but also promote metastasis, which helps breast cancer cells move to other parts of the body.
According to the experts, whose work has been published in Cancer Research, ESR1 is a master regulator of several molecular pathways, including a type of interaction between cells called cell-cell junction. When the researchers took liquid biopsies from patients with mutated ESR1, they found clusters of tumor cells circulating in the blood.
“We believe that this mutation causes tumor cells to become sticky, so they clump together. This is a novel and somewhat unexpected finding,” the experts have detailed, suspecting that these sticky clumps of cells are transported through the blood and are adhere to healthy tissues, promoting new tumors or metastases in other parts of the body.
In the second study, published in Nature Communications, the researchers found that tumors with mutations in ESR1 also had high expression of so-called basal features, which make breast cancers aggressive and difficult to treat.
“Previously, ER+ tumors were thought to be cold or impenetrable by immune cells, meaning they didn’t respond to immunotherapy. But these findings give us a new potential target for patients with ESR1-mutant breast cancer: targeting the macrophages could kill the tumor,” the researchers concluded.
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