Researchers now believe that treating cancer stem cells (CSCs) directly could be the key to preventing relapse and improving survival in endometrial cancer (EC), according to a review published recently in Diagnostics.
CSCs are a small but powerful group of cells within tumors that can self-renew, spread, and survive traditional treatments such as chemotherapy and radiation. They have been linked to tumor regrowth, metastasis, and poor prognosis, making them an important new focus for therapy.
CSCs make up less than 1% of tumor cells but play an outsized role in progression of disease. In endometrial cancer, their presence is associated with advanced stage, deep invasion into the uterus, spread to lymphatic vessels, and reduced overall and disease-free survival.
Markers such as CD133, CD44 and ALDH1 have been linked to more aggressive tumors and therapy resistance. Patients with tumors that express high levels of these markers tend to have worse outcomes, even in early-stage disease.
Read more about the prognosis of EC
“But the plasticity of cancer stem cells still represents an escape mechanism leading to therapy resistance; unfortunately, its inhibition is likely to result in adverse events,” the authors wrote. “A major future challenge is understanding the involvement of this issue in metastasis and therapy resistance.”
Unlike standard tumor cells, CSCs can withstand chemotherapy and radiation because of their “stemness,” which describes the ability to behave like early, undifferentiated cells. This makes them highly adaptable and capable of regenerating tumors after treatment.
Laboratory studies have shown that CSCs in endometrial cancer express genes such as SOX2, NANOG and OCT4, as well as signaling pathways such as Wnt/β-catenin, NF-kB, and Notch, which help them survive and spread.
Targeting these genes, markers and pathways has become a major research priority. Experimental strategies include antibodies against CSC markers, drugs that block critical survival pathways, and immunotherapies such as CAR-T cells aimed at CD133-positive cells.
Patients could eventually benefit from treatments that not only shrink tumors but also remove the cells most likely to cause relapse. Future clinical tools may include liquid biopsies to detect CSCs in the blood and personalized therapy guided by single-cell genetic mapping. While no CSC-targeted therapy is yet standard for endometrial cancer, the approach offers hope for longer-lasting remission and better quality of life.
If these advances translate from the lab to the clinic, patients may face fewer recurrences, more effective treatment options, and improved survival rates, particularly in aggressive or drug-resistant forms of the disease.
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