Project Title: Capitalizing the presence of MAPK pathway alterations in low-grade serous ovarian cancer with next-generation direct pan-KRAS inhibitors
Research Institute: University of Pennsylvania
Principal Investigators: Dr. Dimitrios Nasioudis, MD, and Dr. Fiona Simpkins, MD
Award Amount:  $150,000
Funded by: STAAR Ovarian Cancer Foundation
 
STAAR Low-Grade Serous Ovarian Cancer has awarded $150,000 to a laboratory research study at the University of Pennsylvania for a potential new treatment for low-grade serous ovarian cancer.
 
About half of patients with low-grade serous ovarian cancer have a KRAS genetic mutation that activates what’s known as the RAS/RAF/MAPK pathway. While MEK inhibitors such as trametinib can be effective against this cancer, treatment resistance often occurs.
 
While there already are drugs in development that target specific KRAS mutations, Dr. Dimitrios Nasioudis and his team have identified a new pan-KRAS inhibitor that already has been shown to be effective against LGSOC cell lines.
 
This laboratory study will test the pan-KRAS inhibitor alone and in combination with an estrogen blocker or MEK inhibitor on additional cell lines as well as in organoids and in vivo.
 
“The prognosis of patients with advanced or recurrent LGSOC is poor and patients have limited treatment options,” said Dr. Nasioudis, Assistant Professor of Gynecologic Oncology at the University of Pennsylvania. “Our proposal is designed to capitalize on the unique genomic pathway alterations and hormone receptor expression profile for LGSOC with the goal to bring new effective treatment options into the clinic.”
 
STAAR Low-Grade Serous Ovarian Cancer’s mission is to fund research into potential new treatments for this rare, persistent disease. As the first U.S.-based organization dedicated to LGSOC, we’re working to fill the gap in research funding and drive advancements that will lead to better diagnostic tools, novel therapies, and ultimately, a cure.

Project Title: Analysis of full-length transcripts in low-grade serous ovarian cancer by long-read sequencing
Research Institute: The University of Texas MD Anderson Cancer Center
Principal Investigators: Kwong-Kwok Wong, PhD
Award: $115,580
Funded by: STAAR Low-Grade Serous Ovarian Cancer Foundation and Not These Ovaries
 
Two patient-driven ovarian cancer nonprofit — STAAR Low-Grade Serous Ovarian Cancer Foundation and Not These Ovaries — have jointly awarded a $115,580 research grant to investigate new biomarkers that could improve treatment options for patients with low-grade serous ovarian cancer.
 
Conducted by Kwong-Kwok Wong, Ph.D., professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center,  the laboratory study will use new technology to sequence full-length RNA transcripts in greater detail to identify new gene fusions and biomarkers that could be used to determine whether an LGSOC patient will respond to chemotherapy or endocrine therapy.
  
“This pilot project is exploring a novel technology to perform a more accurate measurement of transcript activities and to discover new genetic markers in LGSOC,”  Dr. Wong said. “As the accuracy of long-read sequencing improves, we are optimistic about the potential in clinical applications for patients who need better options.”
 
Only 20% of LGSOC patients respond to platinum-based chemotherapy, the standard of care for other ovarian cancers. Patients typically undergo surgery followed by chemotherapy and treatment with aromatase inhibitors, which block estrogen production. However, outcomes remain limited due to the unique biology of LGSOC and the lack of personalized therapies.
 
This research will analyze RNA samples from patients who responded to either chemotherapy or endocrine therapy—and those who did not—to uncover new molecular patterns that could guide treatment decisions and lead to more tailored, effective care.
 
“This research directly addresses the gap in options for patients with this rare and underfunded cancer,” said Emily Campbell, Executive Director of Not These Ovaries. “We are proud to invest in innovative science that puts patients at the center of progress.” 
 
“STAAR was founded to drive critical research for a disease that has been overlooked for too long,” said STAAR Chair Nicole Andrews. “We’re excited to collaborate with Not These Ovaries and MD Anderson to accelerate discoveries that could change lives.”

Not These Ovaries is dedicated to quickly funding research and trials to eradicate ovarian cancer, with a focus on understudied and underfunded subtypes that primarily affect younger women. Its transparent model ensures 100% of donations fund immediate research and trials, while also empowering patients and families through education and actionable information.

STAAR Low-Grade Serous Ovarian Cancer’s mission is to fund research into potential new treatments for this rare, persistent disease. As the first U.S.-based organization dedicated to LGSOC, we’re working to fill the gap in research funding and drive advancements that will lead to better diagnostic tools, novel therapies, and ultimately, a cure.

​Project Title: A High-Throughput Screening Program to Discover Combinatorial Treatments Targeting Low-Grade Serous Ovarian Cancer
Research Institute: The University of Chicago
Principal Investigator: Dr. Hilary A. Kenny, Ph.D
Award: $150,000 awarded over 3 years
Funded by: STAAR Low-Grade Serous Ovarian Cancer Foundation
 
STAAR Low-Grade Serous Ovarian Cancer Foundation has award $150,000 over three years to Dr. Hilary A. Kenny at the University of Chicago to conduct high-throughput screening to identify potential drugs to treat LGSOC.
 
At this time, there are no FDA-approved treatments developed specifically for LGSOC. Identifying new therapies is the greatest unmet need in treating this highly recurrent disease. 
 
Dr. Kenny’s research will use 3D models of the LGSOC tumor microenvironment to screen FDA-approved drugs for their ability to kill cancer or impede cancer cell motility. Once the efficacy of these drugs against LGSOC is confirmed in vitro, they will combine these drugs to determine whether an increased synergistic effect can be obtained. 
 
LGSOC is characterized by deep invasion, low proliferation and chemotherapy resistance, and some research has shown it to occur following a non-invasive serous borderline tumor. 
 
“When we began our research into LGSOC, we realized that it was not clear why borderline tumors developed into LGSOC and why they are so deeply invasive, fibrotic, and therapy-resistant,” Dr. Kenny said. “Our team is determined to shift current research and clinical practice paradigms for LGSOC by developing new experimental models to better understand the biology of SBT and LGSOC. We will utilize novel theoretical concepts, approaches, and methodologies to find interventions for treating this therapy-refractory disease.”
 
The 3-year project initially will screen drugs using high-throughput models composed of cancer and stromal cells generated from the University of Chicago’s tissue bank that currently includes 78 patients with LGSOC and 210 with serous borderline tumors. The next stage will test combinations of drugs in 3D human LGSOC in vitro models and in mouse in vivo models of LGSOC, increasing the body of knowledge about potential therapies. 
 
STAAR Low-Grade Serous Ovarian Cancer’s mission is to fund research into potential new treatments for this rare, persistent disease. As the first U.S.-based organization dedicated to LGSOC, we’re working to fill the gap in research funding and drive advancements that will lead to better diagnostic tools, novel therapies, and ultimately, a cure.

Legacy of Hope
​
​Founded in 2020, STAAR has advocated for  patients and families affected by this rare and often under-recognized disease. Our mission is to raise awareness, fund research, and  support everyone impacted by low-grade serous ovarian cancer.

Over the past five years, STAAR has made significant strides in advancing research, improving patient care, and fostering a sense of community among people affected by low-grade serous ovarian cancer. The STAAR Patient Conference was a testament to our commitment to our mission and a celebration of the progress we’ve made.
​

Looking Ahead

As the STAAR Low-Grade Serous Ovarian Cancer Foundation enters our next chapter, we remain dedicated to our mission to improve the lives of people affected by low-grade serous ovarian cancer. The success of our first Patient Conference shows the power of our community and the progress we’ve made in advocacy and advancing research.

With Gratitude

STAAR is an entirely volunteer-run organization, dedicated to advancing research into treatments for LGSOC. We could not have hosted this conference without the generous support of sponsors including Verastem Oncology, Bristol Myers Squibb and Not These Ovaries.  

The first low-grade serous ovarian cancer research to receive funding from STAAR Ovarian Cancer Foundation has been published in the British Journal of Cancer.

STAAR partnered with Cure Our Ovarian Cancer to contribute $70,000 to research by Dr. KK Wong of University of Texas MD Anderson Cancer Center. The research investigated estrogen signaling in low-grade serous ovarian cancer (LGSOC) to better understand how the cancer cells use estrogen. 

“This is a unique opportunity to study the complex and elusive estrogen receptor signaling pathway in low-grade serous ovarian cancer, which would hopefully result in a successful and improved anti-hormone therapy,” Wong said.

FINDINGS

The paper, The Prognostic Value of MEK-pathway associated estrogen receptor signaling activity for female cancers, looked at the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify which may predict endocrine therapy responsiveness.

Because endocrine therapy has been shown to be effective against breast cancer cells, but not reliably against other gynecologic cancers, Wong's research sought to understand the role of ER signaling activity in the development of gynecologic cancers by looking at the difference of the pathway activation between normal and tumor tissues. 

The research found that ER signaling is prognostic for gynecological cancers and that MEK pathway activity is associated with ER signaling in patients with the gynecologic cancers. Targeting both the estrogen receptor and MEK pathways (a chain of proteins associated with cell growth) may aid the development of endocrine therapy strategies. 

IMPLICATIONS FOR LOW-GRADE SEROUS OVARIAN CANCER

"We found that our approach can better predict the response of patients to endocrine therapy, including [those with] LGSOC," Wong said. "In addition, we identified a few genes which are associated with endocrine therapy resistance."

Previous research has shown that hormonal maintenance therapy--such as aromatase inhibitors Letrozole, Anastrozole, and Exemestane—can result in a lower risk of progression in patients with stage II-IV low-grade ovarian serous carcinoma.

The paper also discusses some previous studies into endocrine therapy for ovarian cancer: ​

"Letrozole has been suggested to be valuable as a maintenance treatment of high-grade serous ovarian cancer, especially in patients with chemoresistance or residual disease. Another retrospective study indicates that endocrine therapy could be a practical strategy to postpone subsequent chemotherapy for relapsed high-grade serous ovarian cancer. From a phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors, partial responses were only observed in 14% patients."

"It is important to identify patients who will benefit the most from endocrine therapy and avoid unnecessary treatment for patients who will not respond," Wong said. 

Wong also is researching patient resistance to the MEK inhibitor trametinib in another STAAR-funded study.

LGSOC has fewer treatment options than the more common high-grade serous ovarian cancer. It also tends to be diagnosed in younger patients, with an average age at diagnosis of 45, compared to 62 people for high-grade. Because the cancer cells are slower-growing than high-grade cells, they tend to be resistant to chemotherapy. The average prognosis for LGSOC is about 9 years.

​STAAR Ovarian Cancer Foundation is the only U.S.-based nonprofit dedicated to low-grade serous ovarian cancer. It has contributed more than $500,000 to research low-grade serous ovarian cancer since its founding by three women with LGSOC in 2020. 

The U.S. Food and Drug Administration has granted an orphan drug designation to a low-grade serous ovarian cancer treatment currently in clinical trials—a huge step forward for treating a rare cancer with a high rate of recurrence.  
 
Verastem Oncology received the orphan drug designation for the drug avutometinib alone or in combination with defactinib for the treatment of patients with recurrent low-grade serous ovarian cancer.
 
LGSOC is a distinct ovarian cancer, making up 5-10% of all ovarian cancer diagnoses. While the cancer cells are slower growing than the more common high-grade serous ovarian cancer, LGSOC tends to be resistant to chemotherapy, leading to poor outcomes. It also disproportionately affects younger women, with an average age at diagnosis of 45.
 
Diagnosis is often delayed because LGSOC symptoms can be confused with other illnesses. Symptoms include bloating, feeling full quickly, fatigue, indigestion, menstrual irregularities, changes in bowel habits and painful intercourse.
 
VOICES OF LGSOC
 
The FDA’s orphan drug designation comes on the heels of the first-ever externally led patient focused drug development meeting that STAAR Ovarian Cancer hosted last fall. The meeting amplified the voices of patients with LGSOC and conveyed to the FDA that this is a distinct disease in need of specialized treatment.
 
“Our stories, experiences and advocacy during the meeting served as a powerful catalyst,” said STAAR Board Chair Nicole Andrews. “It brought attention to the urgent need for more research, better treatments, and a deeper understanding of the challenges faced by those with low-grade serous ovarian cancer. Verastem Oncology's orphan drug designation is a direct example of our collective effort, showcasing the real-world impact of patient advocacy.”
 
ORPHAN DISEASES
 
Orphan drug designations are granted to drugs targeting rare diseases with unmet medical needs—such as LGSOC—providing incentives to pharmaceutical companies, including extended market exclusivity and financial incentives, encouraging investment in research and development for rare diseases. 
 
“The FDA Orphan Drug Designation for avutometinib alone or in combination with defactinib in low-grade serous ovarian cancer is an important step in recognizing this rare cancer as a distinct disease that currently has no FDA-approved treatments,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “We are rapidly advancing the development program for avutometinib and defactinib in low-grade serous ovarian cancer with our ongoing Phase 3 clinical trial to deliver this new combination treatment to patients as quickly as possible. We remain on track to begin submission of an NDA to the FDA for Accelerated Approval of this combination in the first half of 2024 and preparing for a potential launch in 2025.”
 
An orphan disease is a rare disease or condition that affects fewer than 200,000 people in the United States and are serious or life threatening. In 1983, the U.S. government passed the Orphan Drug Act to give drug companies financial benefits for developing orphan drugs. This law is meant to help bring more drugs to patients with rare diseases.
 
“This orphan drug designation is a beacon of hope for those with low-grade serous ovarian cancer,” Andrews said. “It encourages pharmaceutical companies to invest in groundbreaking treatments, ultimately transforming the landscape for patients who have long been underserved.”
 
Advantages of Orphan Drug Designations for LGSOC:
 
1. Targeted Therapies: Orphan drug designations facilitate the development of targeted therapies tailored to the unique molecular and genetic characteristics of LGSOC, enhancing treatment precision and efficacy.  
2. Accelerated Approval Process: The orphan drug designation expedites the regulatory approval process, allowing promising treatments for LGSOC to reach patients more swiftly, addressing critical unmet needs in a timely manner.   
3. Research Investment: By incentivizing pharmaceutical companies to invest in LGSOC research, orphan drug designations foster innovation and the exploration of novel treatment modalities, ultimately expanding the therapeutic armamentarium against this rare disease.   
4. Patient Access: Orphan drug designations enhance patient access to innovative treatments by facilitating affordability and availability, ensuring that individuals afflicted with LGSOC have equitable access to potentially life-saving therapies.

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.

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.

​

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.

STAAR Ovarian Cancer Foundation was honored Dec. 1 with an Inspirational Collaboration Award during the third annual World Ovarian Cancer Coalition Impact Awards.

The award celebrates the achievements of organizations that worked in partnership to make a difference in ovarian cancer. STAAR was recognized for its work in two collaborations that brought low-grade serous ovarian cancer into “sharp focus,” said Tristan Bilash, patient advocate and advisor to the World Ovarian Cancer Coalition, who presented the award.

“The first was a multi-stakeholder global survey of those living with a diagnosis of this type, aimed at better understanding the people and circumstances behind the diagnosis. The second major collaboration brought the patient voice to a United States Food and Drug Administration meeting they arranged, and where they met with U.S. officials, researchers, drug companies, and industry. This meeting was the first externally led patient-focused drug development meeting for any type of ovarian cancer, which has the potential of changing the future of drug development and approvals for this disease,” Bilash said.

Nicole Andrews, Chair of STAAR Ovarian Cancer Foundation, said: “Working in a rare cancer space with little funding, patients spread across the globe, and fewer researchers has allowed our board to understand the importance of collaboration for higher impact. This year‘s work helping low-grade serous cancer patients have their voices heard through the international patient needs survey and the Voices of LGSOC event would not have been possible without our global collaboration partners with whom we share this award: Cure Our Ovarian Cancer, World Ovarian Cancer Coalition, and Drs. Gershenson, Sun, Gourley, Grisham, Banerjee, Curry and deFazio—and of course Verastem Oncology, who generously sponsored these projects. Thank you to the World Ovarian Cancer Coalition for their invaluable contributions in promoting global collaborations.” 

Clara MacKay, CEO of the World Ovarian Cancer Coalition said: “With cases set to rise by almost 42% by 2040, the work of advocates who work on behalf of all of those impacted by ovarian cancer is more important than ever. It is truly humbling to see such incredible work achieved over the last year by all of our winners, nominees, and the wider ovarian cancer community.” 

About the World Ovarian Cancer Coalition
The World Ovarian Cancer Coalition is a not-for-profit organization, formally established in 2016, working across the globe towards a world where everyone with ovarian cancer has the best chance of survival, and the best quality of life—wherever they may live. More information can be found on www.worldovariancancercoalition.org

About STAAR Ovarian Cancer Foundation
STAAR Ovarian Cancer Foundation is the only nonprofit in the United States 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.

For more information contact: 
Phaedra Charlton
Director of Communications and Marketing
World Ovarian Cancer Coalition
[email protected]

Nicole Andrews
Board Chair
STAAR Ovarian Cancer Foundation 
[email protected]