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Hormonal treatment for endometrial cancer: Progesterone does not directly target the malignant cells


Progesterone, a female hormone that can be used as a therapy for endometrial cancer, eliminates tumor cells indirectly by binding to its receptor in stromal or connective tissue cells residing in the tumor microenvironment.

Like tumors of the breast and prostate, endometrial cancer is regulated by hormones. Unlike therapies for breast and prostate cancer, where drugs are given to block hormone signaling, in therapy for endometrial cancer progesterone is given to stimulate its hormone receptor. Although it has been used for several decades, no one really knew the mechanisms and site of action for Progesterone therapy.

It is known that a certain subsets of patients will benefit from treatment with Progesterone. However, physicians prescribing the hormone therapy are shooting in the dark because they don't know in advance which patients will respond and which women may have resistant tumors.
Therefore, while Progesterone can be effective as a therapy in endometrial cancer, its use is not widely embraced in clinical practice.

When viewing tumors under the microscope clinicians often focus on the cancer cells and neglect the supporting stroma in the microenvironment. In this study researchers found that all of the Progesterone anti-tumor effects are in fact mediated through the stroma even though it makes up a minor fraction of the tumor.

The results of the three-year study, done using a specially developed laboratory model created by Sanaz Memarzadeh's team that closely mimics human endometrial cancer, was published in the journal of the American Association for Cancer Research.

Memarzadeh and her team showed that if you delete the progesterone receptors in the stromal cells in the tumor microenvironment, Progesterone therapy will not work. However, in a model of hormone resistant endometrial cancer, the tumor cells became sensitive to hormone therapy when the Progesterone receptors are returned to the adjacent cells in the microenvironment.

Going forward, Memarzadeh and her team will translate this work into studies of human samples of endometrial cancer to see if their findings apply to patients. They hope to discover biomarkers that indicate response or resistance to hormone therapy. They also plan to find and test drugs that can reverse progesterone resistance, making cells sensitive to hormone therapy. This approach will provide a potential combination therapy that could prove effective for women with disseminated endometrial cancer.

Currently, the most common treatment for early stage endometrial cancer is hysterectomy, followed by radiation and or chemotherapy. Physicians may prescribe Progesterone to endometrial cancer patients who are seeking to preserve their fertility not knowing whether it will be effective.

Endometrial cancer, which starts in the endometrium or the inner lining of the uterus, is the most common gynecologic cancer in the United States. About 49,000 new cases of endometrial cancer will be diagnosed this year alone, and about 8,000 American women will die from their cancers. The chance of a woman being diagnosed with this cancer in her lifetime is about one in 38, according to the American Cancer Society. ( Xagena )

Source: University of California - Los Angeles ( UCLA ), 2013

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