What We DO:
(excerpted from the MGH Annual Report to The Julie Fund) Over the past year, support from The Julie Fund has played a vital role in advancing women’s cancer research at the Massachusetts General Hospital Cancer Center. We’re pleased to share an update on how your support has made a difference in 2019.
Support for Ovarian Cancer Research The team at the Center for Gynecologic Oncology has continued their work on several ovarian cancer research initiatives over the past year, and has started work on some new areas of research as well. Our team is excited to continue examining the biology of women’s cancers, investigating how genes affect the development of tumors, and identifying novel drug treatments and immunotherapies for ovarian cancer. These efforts are outlined below:
- Developing Galectin-3 Antibodies to Inhibit Ovarian Cancer Growth Galectin-3 (LGALS3) is increasingly being used as a diagnostic biomarker for different cancers. LGALS3 is both unique and essential for linking cancer cells with the stromal microenvironment, and can affect cell development, adhesion, signaling, and immune system interactions. There are currently no approved drugs for this target. Dr. Spriggs’ laboratory is currently working to identify specific antibodies that can inhibit the carbohydrate binding domain of LGALS3 (preventing tumor growth and metastases), and translating these antibodies into a drug that can be used in the clinic to treat ovarian cancer. We believe that these efforts have the potential to have a profound impact on the way we treat ovarian cancers and prevent metastases. Beyond ovarian cancer, there is evidence that LGALS3 plays a central role in the growth and behavior of other tumors (such as prostate, lung and breast) and other inflammatory diseases, including pulmonary fibrosis and congestive heart failure. Funds from The Julie Fund have been used to perform proof of concept studies that are helping us to secure larger grants to support this research.
- Developing New Strategies to Treat Platinum-Resistant Ovarian Cancer Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel drug that targets folate receptor-α, a validated molecular target for therapeutic intervention ovarian cancer. In January 2018 Michael Birrer, MD served as the lead author on a paper analyzing the effectiveness of mirvetuximab soravtansine published in Future Oncology, titled “A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer.” Dr. Birrer and his team found that mirvetuximab soravtansine demonstrated favorable tolerability and encouraging signals of efficacy, most notably in patients with platinum-resistant disease. Funds from The Julie Fund continue to provide important support for our platinum-resistant ovarian cancer research. The Center for Gynecologic Oncology is currently participating in a phase Ib combination trial to evaluate mirvetuximab soravtansine’s activity in the setting of platinum-resistant ovarian cancer. This effort is an exciting example of new agent development at Mass General, and will help us define the role of mirvetuximab soravtansine in the evolving landscape of ovarian cancer therapy.
- Identifying the Genetic Underpinnings of High-Grade Serous Ovarian Cancer Most ovarian carcinomas are classified as high-grade serous (HGS-OvCa), which is the most common and most aggressive histotype. The key to significantly reducing mortality in HGS-OvCa is early diagnosis. While recent research efforts with the Cancer Genome Atlas have provided remarkable insights into the genetic drivers of this disease, we still don’t know much about the genetic make-up of the pre-invasive stages of HGS-OvCa. Dr. Spriggs is currently working with Gad Getz, PhD and Kirsten Kubler, MD, PhD of Mass General and the Broad Institute to examine the genomic landscape of pre-invasive HGS-OvCa lesions and learn about the early events in this disease. The detailed characterization of these curable pre-invasive lesions will enable us to significantly advance preventive medicine and expand the possibilities of early detection in HGSOvCa, ultimately improving survival rates. With support from The Julie Fund and a Department of Defense grant, this project has made significant progress over the last year. HGS-OvCa is a tumor driven mostly by somatic copy number alterations (SCNAs). Preliminary studies have found evidence for genomic disarray in pre-invasive stages of HGS-OvCa in the fallopian tube using traditional low-resolution techniques on a small scale. However, due to the availability of only very small DNA quantities of these tiny pre-neoplastic lesions, no studies have comprehensively analyzed profiles of SCNAs in pre-neoplastic disease on a larger scale. Developments in technology have allowed our team to detect SCNAs using low-input DNA sequence approaches. In addition, we established laser-capture microdissection methods that allow us to generate high complexity DNA sequencing libraries from fewer than 10 cells. As we continue to work on this research, the pairing of these now established top-level sequencing and computing platforms will allow us to gain a deeper understanding of pre-invasive disease and tumor development in HGS-OvCa critical for early detection.
- Recruitment of Oladapo Yeku, MD We are pleased to share that we have recruited Oladapo Yeku, MD to join the Center for Gynecologic Oncology in July 2018. Dr. Yeku joins our Program from Memorial Sloan Kettering Cancer Center, where he focused his research on developing chimeric antigen receptor (CAR) T cell therapies for ovarian cancer. Dr. Yeku’s efforts at Mass General will be focused on building the Gynecologic Oncology Program’s CAR-T cell research program, in collaboration with Mass General’s Cellular Immunotherapy Program. Eventually, we hope to translate his findings into new phase I or phase II clinical trials of CAR T cells for patients with ovarian cancer. Dr. Yeku is currently a fellow in medical oncology at Memorial Sloan Kettering. He graduated summa cum laude with a B.S. degree in biology from Medgar Evers College and was accepted to the Medical Scientist Training Program (MSTP) at Stony Brook University, where he earned his combined MD/PhD degree. While there, he wrote for and was successfully awarded a personal competitive NIH F31 grant to fund his research. After completing his Internal Medicine Residency at University of Pittsburgh Medical Center, he was accepted to Memorial Sloan Kettering Cancer Center’s fellowship program. He is also the recipient of an Ovarian Cancer Research Alliance Award, an institutional NIH T32 Award and an American Society for Clinical Oncology (ASCO) Young Investigator Award. Dr. Yeku’s current research interest is understanding the mechanisms of synergy between IL-12-armored CAR-T cells and immune checkpoint inhibition in ovarian cancer. To do this, he is working on developing a syngeneic immune competent mouse model of metastatic ovarian cancer. This approach will allow us to study the effects of this combination therapy in recruiting and harnessing the hosts’ immune cells against cancer cells. Furthermore, this model will allow us to study the immunosuppressive cytokine, cellular and tumor microenvironment in response to therapy. Funds from The Julie Fund have been used to supplement the costs associated with starting up Dr. Yeku’s laboratory at Mass General.
- Support for Patient Assistance In 2019, The Julie Fund also worked to ensure the availability of financial assistance for women being treated for ovarian cancer and other women’s cancers at the Mass General Cancer Center, Mass General/North Shore Cancer Center, and Vernon Cancer Center at Newton Wellesley Hospital. This support has helped to guarantee the best possible outcomes for patients, regardless of financial situation. The following are some examples of how The Julie Fund made a difference in the lives of these women over the past year: •
- T. is a 56-year-old patient with ovarian cancer. As part of her treatment plan T. is required to come to the hospital every two weeks for an infusion. T. is at the end of her short-term disability pay and is very stressed and concerned about her financial situation. The goal is for T. to return to work when her treatments are completed, but until then she needs help paying her mortgage. With the help of The Julie Fund, Mass General has been able to pay T.’s mortgage. •
- L. is a 75-year-old patient with endometrial cancer. L. also struggles with many other health issues, including acute renal failure. L. lives on a fixed income and has told her social worker that her biggest worry is her ability to pay her monthly rent. Her treatment team was very worried about the impact L.’s financial stress is having on her overall health. L. was grateful that funds from The Julie Fund were made available to pay her rent. The treatment team noticed a difference in L.’s overall stress level when she learned her rent was paid. •
- P. is a 58-year-old patient with breast cancer. P.is a single mother and serves as the main source of financial support for her severely disabled daughter, two other children plus a granddaughter. P. has a well-paying job with excellent benefits, but with multiple surgeries and an aggressive treatment plan she has had to use all of her earned/leave time. P. is also facing more surgery at a later date. P. lost track of her bills and fell behind on her rent. With the help of The Julie Fund, Mass General paid for two months’ rent for P. and her family. •
- L. is a 45-year-old woman with breast cancer. She was working full-time and serving as the primary financial and emotional support for her family – which includes her 6-yearold son, husband, and parents. The familial obligation of supporting her family was deeply rooted in her cultural upbringing. Given her required surgery, chemotherapy, and radiation treatments, she worried extensively about her ability to meet these responsibilities on an emotional, practical, and financial level. Through The Julie Fund, Vernon Cancer Center social workers were able to provide her $350 towards a car loan, which relieved her worry about defaulting on this loan. This support also helped her secure her transportation, which was vital to retaining her employment. The assistance relieved her stress and has allowed her to focus more on her family. •
- K. is a 44-year-old patient being treated for ovarian cancer. She is married with a 5-yearold son, and was working part time as a dental technician. Her husband is employed in a low paying job. They were having difficulty making ends meet during her treatment because she could not return to work. Having a wig was very important to this young woman, however her insurance would not cover it. With help from The Julie Fund, K. was able to obtain a wig from Images Boutique and feel more confident about her appearance. Thank You The Center for Gynecologic Oncology has made incredible progress over the past year, resulting in countless lives saved or extended. Philanthropic funding from The Julie Fund has continued to be vital to advancing this promising research. Your commitment through the above initiatives has made this research possible, and helps support our efforts to better understand and treat women’s cancers. Your support is truly making a difference in the lives of our patients. Looking to the future, the team is optimistic that we will continue to improve treatment options and outcomes for patients and their families. We are fortunate to have you as a partner, and hope you will continue to partner with us as we get ever closer to conquering this disease.
Our Impact: The Julie Fund for Women’s Cancers is the Single Largest Source of Philanthropic Research Funding for Massachusetts General Hospital’s Gynecologic Cancer Research Program. The Fund has raised more than $3.5 million and has impacted thousands of lives through its research funding, support of educational programs, and by providing non-medical expenses for the families of women battling cancer.
The Julie Fund is a registered 501(c)(3) organization.
The Julie Fund, Inc.
PO Box 620-657
Newton, MA 02462