Some patients with uterine leiomyosarcoma may respond to PI3K/mTOR inhibitors

Uterine sarcoma is a rare cancer that occurs when malignant cells form in the muscle and supporting tissues of the uterus. Uterine sarcomas are heterogeneous tumors and usually have an aggressive clinical behavior. Based on the type of cell they developed from, uterine sarcomas can be divided into several different types, including leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma.

The high rates of recurrence and mortality point to the need to find new, more effective therapies. One obstacle is that currently there is no biomarker to predict the response to treatment. Now, an international team identifies a protein as an indicator of poor prognosis for patients with uterine leiomyosarcoma, a form of uterine sarcoma that arises from the smooth muscle lining the walls of the uterus. The study is led by Professor Frédéric Amant at the Netherlands Cancer Institute and is reported in the Clinical Cancer Research.

Prof. Amant and colleagues examined the expression of some promising protein targets in a total of 288 human uterine sarcoma samples. Among the proteins studied, one called P-S6S240 was found in 32% of high-grade tumors and in 9% of low-grade tumors. Besides, patients with leiomyosarcoma expressing P-S6S240 had shorter survival.

The researchers noted that P-S6S240 is involved in the PI3K/mTOR cell-signaling pathway which can drive tumor growth. They tested an experimental PI3K/mTOR inhibitor in mice implanted with human leiomyosarcoma tumors, and found that the mice that responded to the treatment showed basal P-S6S240 expression while the nonresponding model did not show P-S6S240 expression. This indicated that P-S6S240 could predict response to PI3K/mTOR inhibition.
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