Testing Therapies in Mucinous Ovarian Cancer in Novel Patient-Derived Models
Abstract
Mucinous ovarian cancer (MOC) is a rare type of ovarian cancer that is difficult to treat. If caught early, it can be cured by surgery alone, but if it has spread around the body, there are no effective treatments. The usual chemotherapy used for other types of ovarian cancer do not work for MOC. Because this cancer is so rare, it is very difficult to carry out clinical trials just for MOC. Doctors who treat the advanced form of the disease have no MOC-specific guidelines to follow and have to choose chemotherapy without strong evidence to support this choice. We are just beginning to understand MOC at a molecular level. We now know more about the changes in genetic material that are frequent in the tumor cells and cause the cancer to grow. Some of these changes have medicines that target them that are being tested or used in other cancer types. However, we do not know whether these would work in MOC. In addition, there are features of MOC that are unique, so we will need new therapies that have been developed with this cancer type in mind. How can we obtain evidence to support a choice of an existing chemotherapy or targeted medicine? How can we find new targets for therapy and get these into the clinic? This proposal will take a multi-pronged approach to cover several avenues of investigation. We will: (a) Test existing therapies using patient cells that are grown in the laboratory (b) Discover and test new therapies using information we have obtained on the molecular profile of MOC. (c) Test combinations of therapies to find synergies. (d) Evaluate whether the therapies or combinations are effective on cells from patients that grow as tumors in mice. The current proposal is a natural extension of our DOD pilot study. We were funded to generate new “models” of MOC – cells from patients that are grown in the laboratory, either in plastic flasks or using new 3D methods that are more similar to how the tumor grows in the body. We were also funded to develop models where the tumor cells are grown in mice. The purpose of generating these models was always to go on and use them to test therapies for MOC in order to provide evidence for efficacy. Any existing therapy shown to be effective in our study would have a massive and direct impact for women with MOC, as it could be immediately translated to the clinic. Because there are no MOC-specific guidelines for recurrent disease, clinicians may choose any chemotherapy approved for solid tumors. This study will provide evidence to support a chemotherapy choice. Targeted therapies may also be provided if the target is present; some evidence for efficacy in the tumor type is available (even preclinical data is helpful for a drug approved in another tumor type), and the pharmaceutical company is willing to provide access. Therefore, women with MOC would be more likely to receive a therapy that helps in managing their disease rather than suffering the side effects of a therapy that did not work. For targeted therapies that are still in clinical trials in other cancer types, our study will provide evidence to persuade those running trials to include MOC in them and to raise awareness among doctors that this could be an option for their patient. This awareness is especially important for “basket” trials, where multiple compounds are being tested in a set of tumors based on the tumor molecular profile (for example after genetic testing of the tumor). It would be straightforward to include MOC in such studies, given the strong rationale that our data could provide. Completion of our discovery aim will identify new therapeutic leads that can then be further tested for efficacy and toxicity in the mouse models that we are developing. These targets may have wider implications for cancers with similar molecular profiles, such as pancreatic cancer. Testing molecules in additional models for diverse cancer types may broaden the pool of cance
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110496
Entities
People
- Kylie Gorringe
Organizations
- United States Army
- University of Melbourne