Endometrial Cancer Research
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One research goal at the G.O. Discovery Lab is to improve the way we treat patients with gynecologic cancers. As part of this goal, we are looking for effective and better tolerated therapies for endometrial cancer.
Endometrial cancer (a form of uterine cancer) is the most common gynecologic cancer in the U.S. It originates from the endometrium, a specialized and hormonally sensitive cell layer that lines the inside of the uterus. When the endometrium becomes abnormal the cells over grow inside the uterus leading to formation of hyperplasia (crowded abnormal cells) and ultimately cancer. While endometrial cancer is often curable if detected in early stages, the side-effects of current therapies (surgery, radiation and chemotherapy) can have life-long debilitating effects. These standard treatments may be ineffective in patients with later stages of endometrial cancer, where the disease has returned or spread to other organs. Currently, patients in their child-bearing years who would prefer to preserve their uterus often have no choice but to undergo a hysterectomy, destroying their fertility.
Hormonal therapy is an alternative treatment in endometrial cancer that could potentially avoid many negative side-effects of the current treatment regimens. Just like breast and prostate cancer, endometrial cancers can be responsive to hormonal treatment But while hormonal treatment has been very successful in treating patients with breast and prostate cancer, it is not widely used in patients with endometrial cancer. The main reason is lack of research in the field.
Progesterone is easily administered, has few side-effects, is relatively inexpensive, and is available even to patients with limited access to health care. The progesterone hormone can be an effective treatment for up to 50% of patients with endometrial cancer. This means that half of endometrial cancer patients have tumors that will regress when treated with progesterone, while the other half have tumors that will continue to grow when they are given progesterone. At the moment, physicians have no way to determine which endometrial tumors will respond to progesterone therapy, so treating a patient with progesterone is a lot like tossing a coin and trying to call “heads or tails”. Doctors also do not understand exactly how progesterone cures endometrial tumors. For these reasons, progesterone therapy is not commonly used in treating endometrial cancer.
We aim to change this by developing a simple biopsy-based office test that can predict if a patient’s endometrial cancer can be successfully treated with progesterone. We are also exploring ways to make progesterone resistant tumors respond to therapy.
Using a model system developed in our laboratory, we are examining genetic changes in the two major cells types (epithelial and stromal cells) of endometrial tumors. We then determine how these changes influence the response of the cancer to progesterone therapy. We hope to utilize the answer we gain from this model to analyze patient tumors and potentially predict which ones will respond favorably to progesterone therapy.
How will we do this? Endometrial biopsies are routinely collected at the doctor’s office during an outpatient visit as a way to diagnose endometrial cancer. When a patient agrees to be in our institutional review board approved study, we can take a portion of the biopsy back to our laboratory where the epithelial cells are separated from stromal cells. DNA and RNA is extracted from the isolated cells, saved and analyzed for genetic changes commonly associated with endometrial cancer. Based on results from our model, we can make an initial predication on how each patient will respond to progesterone treatment.
This is being done with patients who are currently being treated with progesterone by their doctor. We follow the course of their treatment to determine how effective progesterone is in destroying their tumors. Once we know how these women’s tumors respond to progesterone therapy, we can compare the genetic profile of their tumor with their progesterone response and predictions from our model. As we gather more information, we can improve our predictions until ultimately we can determine which patients can be successfully treated with progesterone based just on a simple biopsy.
Our findings may provide:
Only in this way can we develop efficient and effective screening measures for response to progesterone, and create the tools to do so during a clinical visit. Findings will ultimately help improve lives of thousands of women diagnosed with endometrial cancer and hyperplasia by offering an effective treatment that is much better tolerated compared to current radical treatments.