Can Patient-Derived Ovarian Cancer Organoids Aid in Treatment Selection?
Posted: Wednesday, November 21, 2018
Many high-grade serous ovarian cancers are weakened by drugs that target the tumor cells’ ability to repair genetic damage. However, it is difficult to predict which patients’ tumors will be sensitive to platinum drugs and other therapies. Sarah J. Hill, MD, PhD, of the Dana-Farber Cancer Institute, Boston, and colleagues successfully developed organoid cultures from patients with these tumors that may be able to predict their sensitivity or resistance to chemotherapy more accurately than DNA sequencing. Unlike other types of solid tumor organoids, which can take weeks or months to form, the ovarian cancer organoids grew in just 7 to 10 days. The study findings were reported in Cancer Discovery.
“Because these ovarian tumor organoids grow out so quickly, we can do rapid, direct tests of drugs and combinations of drugs to predict a patient’s response,” said senior author Alan D’Andrea, MD, Director of Dana-Farber’s Susan F. Smith Center for Women’s Cancers, in an institutional press release.
When the researchers tested 33 organoid cultures originating from 22 patients with high-grade serous ovarian cancers, they found the organoids closely matched the genetic composition of the patients’ tumor and did not acquire new mutations. Regardless of DNA-repair gene-mutation status, a functional defect in homologous recombination in the organoids correlated with PARP inhibitor sensitivity, whereas a defect in replication fork protection correlated with carboplatin and CHK1 and ATR inhibitor sensitivity.
They also discovered that most of the organoid cultures (94%) were not sensitive to the PARP inhibitor olaparib, even though genomic testing indicated that many of them would have these defects. “Although the low rate of PARP inhibitor sensitivity is surprising, our results are more accurate than genetic predictions alone,” stated Dr. Hill.