Organoid model provides platform for scientists to study factors that lead to cancer development in BRCA1 mutation carriers

Beth Y. Karlan, MD, Professor of UCLA Obstetrics and Gynecology, Vice Chair of Women's Health Research, and the Director of Cancer Population Genetics at  UCLA Health Jonsson Comprehensive Cancer Center, co-led a study in which cancer researchers and stem cell scientists used cells from ovarian cancer patients who carried a BRCA1 mutation to create organoids that mimic fallopian tubes.

“From peripheral white blood cells that were immortalized – manipulated to proliferate indefinitely – we made induced pluripotent stem cells,” Dr. Karlan said. “We then created conditions for those cells to differentiate into organoids that recapitulate the serous fallopian tube cells that are the origin of ovarian cancer.”

Beth Karlan, MD Lab

Dr. Karlan said the findings, published in Cell Reports, offer several opportunities for researchers. The organoid model provides a platform for scientists to study factors that lead to cancer development in BRCA1 mutation carriers as well as factors that might prevent transformation to cancer. It also enables researchers to test therapeutic interventions on organoids that recapitulate ovarian cancer.

The study supports recent research suggesting that ovarian cancer most frequently originates from the cells lining the fallopian tubes. In fact, compared to organoids created from healthy women without a BRCA1 mutation, the organoids with the BRCA1 mutation spontaneously developed multiple cellular abnormalities that are consistent with cancer development.

“The establishment of fallopian tube organoids created from women with and without BRCA1 mutations may help predict when and which women will develop ovarian cancer and help identify interventions that may be able to prevent cancer,” Dr. Karlan said.

“Currently, surgery to remove the fallopian tubes and ovaries is the most effective preventative intervention," she said. "But these fallopian tube organoids provide a model that contains all the genes of the person who provided the blood sample, and they can be used to test the effectiveness of multiple drugs or combinations of drugs to prevent the development of cancer. This is a major step toward our ultimate goal of providing truly personalized medicine and precision prevention.”

Dr. Karlan is hopeful that this advancement and highly innovative work will rapidly translate to the discovery of targeted ways to both prevent and treat ovarian cancer.