Taking Ovarian Cancer Maintenance Therapy to the Next Level
Abstract
Women in the general public and military service who are treated for ovarian cancer can be cleared of their cancer with surgery and chemotherapy, but most often their cancer comes back. After completion of surgery and chemotherapy, doctors treat patients with a treatment called maintenance therapy to increase the time it takes for their cancer to come back. Once the cancer returns during maintenance therapy, patients are treated again with chemotherapy, but the cancer keeps coming back and the chemotherapy is less effective on each subsequent round of treatment. Often additional rounds of maintenance therapy are no longer able to keep the cancer at bay. Even before the cancer comes back, patients often experience severe side effects from the maintenance therapy and have to stop. Thus, new and less-toxic maintenance therapies are needed. This is an area of high unmet need in which our novel investigational drug, SHetA2, has demonstrated much promise as an active and well-tolerated intervention. In laboratory studies, SHetA2 did not cause side effects or toxicity at doses 50-fold above doses shown to prevent and inhibit cancer growth. Thus, it is expected that SHetA2 will cause no or less side effects to current drugs being used in ovarian cancer maintenance therapy. Since SHetA2 capsules can be taken by mouth, ovarian cancer patients on SHetA2 maintenance therapy can take their daily drug in the comfort of their own homes, without having to go into the clinic for IV infusions of drug. We anticipate that SHetA2 maintenance therapy will, without causing side effects, increase the amount of time before ovarian cancer patients experience cancer recurrence. This is because SHetA2 was able to do this in a mouse model of ovarian cancer maintenance therapy. With this preliminary finding, we now need to understand more about how SHetA2 is doing this and what doses are most effective. The information of how SHetA2 works and how much is needed to prevent cancer recurrence is needed in order to design clinical trials testing SHetA2 in ovarian cancer maintenance therapy. This proposed research project is designed to develop this needed understanding of how SHetA2 inhibits ovarian cancer recurrence. Recurrence is believed to be caused by clumps of ovarian cancer cells in fluid called ascites that builds up inside the belly of patients. Ovarian cancer cell clumps will be collected from ascites specimens donated by ovarian cancer patients, treated with SHetA2 in the lab and studied for how they react to this treatment at the molecular and cellular levels. Normally, these specimens are looked at by pathologists and then thrown away. This study will allow these discarded specimens to be put to good use in research. This study will compare how SHetA2 changes molecular and cellular aspect of the ovarian cancer cells with this drug’s effect on the cell’s abilities to form metastases (additional tumor growth sites in the body). These molecular and cellular effects that are altered by SHetA2 inhibition of metastases will be identified. These identified molecular effects will then be studied to confirm their role in SHetA2-inhibition of metastases by testing whether preventing the molecular effect also prevents the inhibition of metastases by SHetA2. This project will also study ways that SHetA2 can be combined with other drugs to be even more effective at increasing the time to ovarian cancer recurrence without causing side effects. Findings will be also studied in mouse models of ovarian cancer maintenance therapy to confirm that the results we observe in cell cultures also occur inside the body. Another goal of this project is to optimize a technology called single spheroid mass spectrometry that will allow measurement of drug concentrations inside clumps of ovarian cancer cells. At the same time, this technology will allow the measurement of SHetA2 effects on fat burning inside the ovarian cancer cells. Fat bu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310176
Entities
People
- Anthony Burgett
Organizations
- United States Army
- University of Oklahoma Health Sciences Center