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Project Title: Targeting trametinib-resistant low-grade serous ovarian cancer by drug repurposing
Research Institute: MD Anderson Cancer Center Principal Investigator: Dr. Kwong K. Wong Ph.D., Professor Estimated Cost for Project: $76,000 Funded by: STAAR Ovarian Cancer Foundation STAAR Ovarian Cancer Foundation has awarded $76,000 to Kwong K. Wong, Ph.D., professor of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center, to learn more about trametinib adaptive resistant low-grade serous carcinoma (LGSOC) cell lines, and identify therapeutic agents to overcome resistance. With STAAR’s support, Wong and his team are investigating whether targeted drug therapy can suppress trametinib resistance in patients with LGSOC. “We are excited to be able to screen thousands of existing drugs for repurposing their current uses to overcome trametinib resistance in LGSOC,” Wong said. “These drugs include approved, discontinued and investigational therapeutics for other diseases. This approach could be faster and more cost effective than developing a new drug for treating patients who currently fail trametinib treatment but with very few other options.” LGSOC has fewer effective treatment options than high-grade serous ovarian cancer. The MEK inhibitor trametinib has shown promising results when LGSOC does not respond to chemotherapy or aromatase inhibitors. Research found initial tumor shrinkage in approximately 26% of patients. Unfortunately, patients can develop a resistance to the drug over time, allowing the disease to progress. Sara Vellve was diagnosed with LGSOC in 2015 at age 50, and participated in a trametinib trial in 2017. “At first I had adverse reactions, but after a dose reduction, I was stable for six months before my disease progressed,” she said. Since then, Vellve has continued to participate in trials to find the most effective treatment for her cancer. “There are too few treatment options for low-grade serous ovarian cancer. If this study could find a workaround to trametinib resistance, it would be a tremendous step forward in disease management.” Wong is testing the efficacies of 10-15 drugs that might suppress the growth of trametinib adaptive resistant LGSOC cells. He will investigate how these drugs overcome the adaptive resistance using both LGSOC cell culture and LGSOC mouse models. Once the trametinib adaptive response is deciphered, clinical trials can combine targeted therapy and repurposing drugs to improve LGSOC patient survival. More importantly, this study will generate critical data to support novel clinical trials with repurposing drugs for LGSC patients who develop trametinib resistance. Drug repurposing could also reveal new biomarkers and pathways that can be targeted for LGSOC. LGSC is a rare subtype of ovarian cancer, making up fewer than 10% of ovarian cancer cases. The average age at diagnosis is 45, and the average length of survival is about 9 years. STAAR Ovarian Cancer Foundation is the only U.S.-based nonprofit dedicated to low-grade serous ovarian cancer. It was co-founded by three women with LGSOC in early 2020. The foundation works with the global charity Cure Our Ovarian Cancer to advance research opportunities in the United States to find better treatment options for LGSOC.
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