Lan Gardner Coffman, MD

Lan Gardner Coffman, MD

About Project

RISING STAR GRANT


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


PROJECT 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 environment 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 cancel cell survival, growth, and spread. ovarian cancer cells appear to convert normal tissue mesenchymal stem cells in the ovary into CA-MSCs through “re-programming” of these cells. EZH2 appears to be a critical factor which leads to cancer cell reprogramming of CA-MSCs. Through blocking the actions of EZH2, we may be able to prevent the formation of this tumor supporting soil thus preventing the survival of cancer cells. 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.


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