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]

Project Title: Identifying Predictors for Chemosensitivity in Patients with Advanced and Recurrent Low-Grade Serous Ovarian Cancer 
Research Institute: Memorial Sloan Kettering Cancer Center, Gynecologic Medical Oncology and Pathology services.
Co-Principal Investigators: Rachel Grisham, MD; M. Herman Chui, MD, FRCPC
Estimated Cost for Project:  $150,000 for 1 year of funding or $250,000 for 2 years of funding 
Funded by: STAAR Ovarian Cancer Foundation

​Research at Memorial Sloan Kettering Cancer Center (MSK) seeks to predict whether low-grade serous ovarian cancer (LGSOC) patients will respond to chemotherapy.
 
Studies have shown that cytotoxic chemotherapy is less effective for LGSOC patients than it is for people with high-grade serous carcinoma, but some LGSOC patients do respond to chemotherapy.
 
Without a reliable predictor, the standard of care for both types of cancer typically has been the same: primary debulking surgery followed by adjuvant platinum/taxane based chemotherapy.
 
STAAR Ovarian Cancer Foundation has awarded $250,000 to MSK’s Rachel N. Grisham, MD, and M. Herman Chui, MD, FRCPC, to develop a panel of biomarker tools to predict which patients are most likely to respond to chemotherapy.
 
The research will help patients and doctors make treatment decisions and avoid unnecessary toxicity for those unlikely to benefit from chemotherapy.
 
“I was devastated when I learned that my cancer had no response to three rounds of chemotherapy,” said STAAR board member Kari Neumeyer, a LGSOC survivor who was diagnosed at 44 years old. “This research could prevent women like me from having to go through unnecessary chemotherapy. I was fortunate that my surgeon removed all of the cancer. If I knew then what I know now, I would have chosen not to undergo chemo.”
 
MSK’s Grisham and Chui will analyze the differences in tissue from patients who responded to chemotherapy and those who did not. Targeted panel sequencing will assess cancer driver mutations and measures of genomic instability such as mutation counts, fraction of genome altered by copy number changes, and frequency of intrachromosomal breakpoints.​

“I am incredibly grateful to STAAR Ovarian Cancer Foundation for their dedication and fundraising efforts,” Grisham said. “Low-grade serous ovarian cancer is a clinically and molecularly unique disease that requires dedicated research and studies to develop an individualized treatment approach.”
 
"Because of its rarity, low-grade serous ovarian cancer is historically an underfunded area of research,” Chui said. “This generous grant is integral for us to further study the biology of this disease and to develop novel molecular tools to help guide treatment.”
 
The research will set the foundation on the molecular basis for chemotherapy resistance in LGSOC, which could form the basis of future work to develop novel therapeutic strategies.
​
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.
 
About the Investigators:  
 
Herman Chui is a gynecologic pathologist in the Department of Pathology and Laboratory Medicine at MSK. He has a particular interest in the molecular pathogenesis of ovarian serous borderline tumor and low-grade serous ovarian cancer, engendered since his fellowship training at the Johns Hopkins Hospital, where he developed expertise and appreciation for the diagnostic subtleties and unique biology of this complex and unusual disease.
 
Rachel Grisham is the section head of Ovarian Cancer Research and Treatment at MSK . She is committed to the development of novel treatment strategies for women with rare tumors. Her research has focused on the accelerated development of more effective and better tolerated treatment strategies for people with low-grade serous ovarian cancer. She serves as the Precision Therapeutics Chair for the International Consortium for Low-Grade Serous Ovarian Cancer (ICLC), serves on the Rare Tumor Committee for NRG, and has been the principal investigator for multiple clinical trials focused on novel therapeutics for low grade serous ovarian cancer and other rare tumors.
 
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.

Project title: Estrogen Signaling in Low-Grade Serous Carcinoma (LGSOC)
Research Institute: MD Anderson Cancer Center
Lead Researcher: Dr. KK Wong PhD, Professor
Start date: June 2021
Project cost: $70,000
Funded by: STAAR Ovarian Cancer Foundation and Cure Our Ovarian Cancer

STAAR Ovarian Cancer and international partner Cure Our Ovarian Cancer are proud to announce the funding of their first US based research grant at MD Anderson Cancer Center.

STAAR Ovarian Cancer and Cure Our Ovarian Cancer have jointly contributed $70,000 to the project entitled: Estrogen Signaling in Low-Grade Serous Carcinoma (LGSC). The project seeks to better understand how LGSC can use estrogen to grow and spread – and identify potential targets to improve treatment options.

“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,”  said Dr. KK Wong of MD Anderson Cancer Center.

Estrogens are major regulators of growth and differentiation in normal ovaries and potentially play a role in the development and progression of ovarian cancer, but the mechanisms of action remain unclear.

The actions of estrogens on ovarian tissue are mediated by estrogen receptors. There are two major types of estrogen receptors – ERα and ERβ. Furthermore, multiple variants of the ERα have been identified in LGSC. The types of estrogen receptors found in LGSC are different from those in normal ovary.

Hormonal maintenance therapies (HMT) have improved the progression-free survival of patients with recurrent low-grade ovarian cancer, but unfortunately, these treatments have not achieved comparable results as in breast cancer.

Preliminary data suggests that estrogen signaling is unique in low-grade serous cancer, and there is a need to further explore and understand the mechanisms underpinning it, which could provide new and clinically relevant insights regarding the role of estrogen in low-grade serous ovarian cancer.

Researchers will use advanced genetic sequencing and laboratory techniques to identify the specific type of estrogen receptors involved in LGSC (which they think will differ from breast cancer) and investigate the molecular and genetic characteristics involved in its expression.

The study has the potential to find biomarkers to predict response to HMT, in addition to insights which researchers hope will guide future research to help HMT work better.

Funds from the 2020 September Step Up event along with and hundreds of generous members of the public, helped make this grant possible. Nicole Andrews, who hosted a Step Up Challenge in her hometown prior to joining STAAR's Board of Directors shared her experience:

"Being diagnosed with Low Grade Serous Cancer (LGSC), a rare form of ovarian cancer, was shocking. I felt scared, shut down, and out of control. The Step-Up Campaign gave me the opportunity to transform my thoughts and fears into constructive energy and focus on creating a positive future. I’m honored that my friends and family “stepped up” alongside me and helped me exceed my fundraising goal. While it’s unusual to know how funds you raise are used, I was thrilled to learn our donations are already working to help researchers understand why and how LGSC uses estrogen so that enhanced treatment options can be developed. My deepest thanks to all working tirelessly to improve outcomes for LGSC survivors, bringing invaluable hope and healing to me and my fellow LGSC sisters."

MD Anderson Cancer Center are world leaders in low-grade serous carcinoma (LGSC) research. They were instrumental in helping identify LGSC as a unique cancer in 2004. In addition, their research has formed the basis for many of the current LGSC treatment recommendations. In 2018, they added LGSC to their Cancer Moon Shots Program.

Cure Our Ovarian Cancer (COOC) is a global charity dedicated to improving the survival of people with LGSC through research. It was founded in 2018 by New Zealand woman Jane Ludemann following her diagnosis. Today COOC supports researchers in five countries, including the United States of America.