Lan Gardner Coffman, MD, PhD

Lan Gardner Coffman, MD, PhD

Lan Gardner Coffman, MD, PhD

About Project

RISING STAR GRANT


TARGETING THE FORMATION OF CARCINOMA-ASSOCIATED MESENCHYMAL STEM CELLS TO PREVENT THE ESTABLISHMENT OF THE OVARIAN CANCER MICROENVIRONMENT


PROJECT & PROGRESS SUMMARY

Ovarian cancer is the deadliest gynecologic cancer due to late diagnosis without effective preventative strategies. The majority of factors which lead to cancer cell development are things we cannot change such as the genes we inherit from our parents or environmental stresses. However, in order for ovarian cancer cells to survive and cause wide-spread disease, the tumor cells must find a supportive environment or “soil” where the cancer cell “seeds” can grow. This “soil” provides critical nutrients and protects the cancer cell “seeds” from being destroyed by the immune system. Cancer cells create this supportive “soil” by changing normal tissues into cancer supporting tissues. One critical cancer supporting cell is the carcinoma-associated mesenchymal stem cells (CA-MSCs) which support cancer cell survival, growth and spread. Ovarian cancer cells convert normal tissue mesenchymal stem cells in the ovary into CA-MSCs through “re-programing” of these cells. Our work over the last year demonstrates that EZH2, a protein that dictates cell behavior through a process called “epigenetic regulation,” is critical to the cancer cell reprograming of CA-MSCs. We have shown that blocking the actions of EZH2 prevents the formation of a CA-MSC. Importantly, by blocking the formation of a CA-MSC, we can decrease the ability of cancer cells to find supportive soil. In a mouse model, a drug that blocks EZH2 in MSCs reduced the formation of cancer within the ovaries by 60%. We are still studying how cancer cells cause EZH2 to turn a normal MSC into a CA-MSC but our results thus far are promising. Overall, treatments which block the conversion of normal tissue into cancer supporting soil could help prevent the development of wide spread cancer in high risk women who have not had removal of their fallopian tubes and ovaries or those where premalignant cells have been identified. Preventing the development of a supportive tumor microenvironment is a unique and potentially powerful approach to preventing ovarian cancer.


Back to Current Research