Project Summary/Abstract
Women undergoing chemotherapy treatment for ovarian cancer (OC) can develop new peritoneal metastases
during recovery time, indicating a possibility that therapy promotes the evolution of metastatic cell populations.
Therefore, it is of the highest clinical interest to study the effects of chemotherapy on peritoneal dissemination.
A hallmark of OC peritoneal dissemination is a disruption of tumor tissue that leads to the formation of carcinoma
outgrowths that subsequently detach, transit into the peritoneal cavity, and intercalate into mesothelium that
covers vital organs. In this application, we hypothesize that chemotherapy disrupts tumor tissue, promotes
outgrowths, cell detachment, and tumor mesothelial intercalation. To test our hypothesis, we propose two Aims
that center on the development of in vitro and in vivo imaging approaches that will enable visualization and
quantification of OC dissemination post-chemotherapy.
In Aim 1 of this project, we will establish an organoid-based imaging assay to determine the effects of
chemotherapy on OC organoid structure, outgrowth formation, cell detachment, and mesothelial intercalation.
Aim 2 of this proposal focuses on developing an in vivo imaging assay in a mouse model to study the dynamic
activities of OC in response to chemotherapy. To complete these aims, we have assembled an interinstitutional
team with members that bring unique expertise in tissue engineering of OC dissemination, 3D in vivo imaging of
the mouse reproductive system, and genetically modified models of ovarian cancer. This multi-PI combined
efforts will provide much-needed information about the effects of chemotherapy on the dynamics of OC
peritoneal dissemination.