The goal at the G.O. Discovery Lab is to improve the way we treat patients with gynecologic diseases. As part of this goal, we are looking for effective and better tolerated therapies for these diseases, including serous ovarian cancer and endometrial cancer.
One of our major projects is looking at new treatments for serous ovarian cancer. Ovarian tumors account for about 3% of all malignancies in women and serous tumors are the most common form of ovarian cancer. They are called “ovarian” because they are often found implanted on the surface of the ovary. However, recent work from our laboratory and other researchers suggests that serous tumor do not arise from the ovary, but actually may originate from cells lining the fallopian tube.
The standard of treatment for serous ovarian cancer is surgical removal of the tumor followed by chemotherapy. However, this is not always effective and many patients see relapse of a chemotherapy resistant tumor. The clinical behavior of this disease suggests that subsets of serous tumor cells must be resistant to existing therapies. These chemotherapy resistant tumor cells may acquire properties of stem cells and/or originate from normal stem cells. These cells comprise a small fraction of the serous tumor but are the cancer initiating cells (i.e. the mother tumor cells that give rise to the rest of the tumor). Given their resemblance to normal stem cells, they are called cancer stem cells.
In order to eradicate serous cancers, it is our goal to find a way to target the serous cancer stem cells either killing them directly or indirectly by introducing an agent to sensitize these serous cancer stem cells to standard treatments.
Our second project focuses on determining predictors of response of endometrial cancer, a form of uterine cancer and the most common gynecologic cancer in the U.S., to hormonal therapy. Endometrial cancer 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. Furthermore, 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. 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 due to a 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. 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.
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. Research/Clinical Interest:
Designing clinical trials for patients with Ovarian Cancer having surgery at UCLA. Link to my Recent Pubmed Publications.