Project Title: Targeting trametinib-resistant low-grade serous ovarian cancer by drug repurposing (expanded study)
Research Institute: University of Texas MD Anderson Cancer Center
Principal Investigator: Kwong K. Wong Ph.D., Professor
Estimated Cost for Project:  $53,000
Funded by: STAAR Ovarian Cancer Foundation

STAAR Ovarian Cancer Foundation has awarded $53,000 to Kwong Kwok Wong, Ph.D, to expand research funded in 2022 to investigate a novel mechanism of trametinib-adaptive resistance and a potential therapeutic approach. 

A professor of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center, Wong is studying whether a BET bromodomain inhibitor will be effective in combination with trametinib against resistance.

The MEK inhibitor trametinib can be effective in patients when chemotherapy or aromatase inhibitors have failed, but many patients develop adaptive resistance to the drug.

“Using two pairs of trametinib-sensitive and adaptively resistant LGSOC cell lines for drug screening previously supported by STAAR Ovarian Cancer Foundation, we found that adaptively resistant cells are more sensitive to BET bromodomain inhibitors than their parental cells,” Wong said. 

LGSOC has fewer effective treatment options than high-grade serous ovarian cancer. Wong’s study will generate critical data to support the development of BET inhibitor, particularly for LGSOC patients in whom treatment with Trametinib has failed.

LGSOC is a rare 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.

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Project Title: Endocrine and mTOR therapy in recurrent low-grade serous ovarian cancer
Research Institute: Stephenson Cancer Center at the University of Oklahoma Health Sciences
Principal Investigators: Doris M. Benbrook, PhD, and Christina Washington, MD
Estimated Cost for Project:  $100,000
Funded by: STAAR Ovarian Cancer Foundation

STAAR Ovarian Cancer Foundation has awarded $100,000 to researchers at the Stephenson Cancer Center at the University of Oklahoma Health Sciences for a Phase 2 clinical trial to identify patients whose low-grade serous ovarian cancer (LGSOC) might respond to combination treatment of the mTOR inhibitor nab-sirolimus and the estrogen blocker Fulvestrant.

LGSOC cells are molecularly different from high-grade serous ovarian cancer cells and do not respond to the same treatments. Response to mTOR inhibitors has not been well studied compared to other LGSOC treatments, but clinical research has shown a synergistic effect when combined with endocrine therapy in hormonally driven cancers such as LGSOC.

The co-principal investigators are Doris M. Benbrook, PhD, a Presbyterian Health Foundation Presidential Professor tenured in the University of Oklahoma College of Medicine Section of Gynecologic Oncology, and Dr. Christina Washington, MD, Assistant Professor in the University of Oklahoma College of Medicine Section of Gynecologic Oncology, who is being mentored by internationally renowned clinical trialist Kathleen Moore, MD.

The researchers will collect and sequence the DNA of biopsies from patients enrolled in the trial to determine if genetic alterations can predict which patients would most likely benefit from the combined treatment and to gain greater understanding of the molecular determinants of low-grade serous ovarian cancer.

“I believe that our research will produce results and generate new hypotheses that can be studied and validated in future trials to improve the outcomes of women suffering from low-grade serous ovarian cancer,” Dr. Benbrook said.

STAAR Ovarian Cancer Foundation is the only U.S.-based nonprofit dedicated to low-grade serous ovarian cancer. It was founded in 2020 by three women with LGSOC.