Victoria’s Secret Global Fund for Women’s Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR supports female midcareer scientists conducting innovative research in breast and gynecologic cancers and globally fosters innovation in the understanding, prevention, interception, early detection, diagnosis, and treatment with the goal of eliminating cancer health disparities and improving patient outcomes.

2023 Grantees

Research

Central nervous system metastases occur frequently in breast cancer, with few effective systemic therapy options.  Historically, we have had a limited understanding of the molecular underpinnings driving metastasis to the brain from breast cancer. There is an urgent need for more focused efforts to study the biology of brain metastases, develop pre-clinical models that recapitulate the metastatic process, and identify improved therapeutics for this disease.  The objective of our study is to comprehensively characterize the constellation of epigenetic and genetic alterations associated with brain metastases from breast cancer and to functionally characterize the role of these alterations in the metastatic process in in vivo models of metastasis. Our overarching scientific premise is that characterizing the molecular features of brain metastases will elucidate fundamental biology, allowing us to identify novel therapeutic strategies.

Biography

Originally from Vancouver, BC, Dr. Priscilla Brastianos completed her medical school and internal medicine residency at Johns Hopkins School of Medicine and fellowship training in hematology/oncology and neuro-oncology at the Dana-Farber Cancer Institute and Massachusetts General Hospital/Harvard Medical School. She is now director of the Central Nervous System Metastasis Center at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School. She leads a multi-R01-funded laboratory, and her research focuses on understanding the genomic mechanisms that drive primary and metastatic brain tumors. She has lead studies which have identified novel therapeutic targets in primary and metastatic brain tumors, and she has translated her scientific findings to national multicenter trials. She also leads a multidisciplinary central nervous system metastasis clinic at Massachusetts General Hospital/Harvard Medical School. She has received a number of awards for her work including a NextGen Star Award by the American Association for Cancer Research, a Damon Runyon Clinical Investigator Award, a Breast Cancer Research Foundation Award, a Susan G. Komen Career Catalyst Award, the American Brain Tumor Association Joel Gingras Award, the Anne Klibanski Award for Excellence in Mentorship, and the Society for Neuro-Oncology’s Women in Neuro-Oncology Mid-Career Exemplary Physician Award.

Acknowledgement of Support

I am very grateful for this Victoria’s Secret Global Fund for Women’s Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR. Brain metastases remain an unmet need in oncology. With funding from this grant, we hope to make great strides at identifying better therapies for patients with this devastating disease.

Research

Black individuals face multi-level barriers to early diagnosis of endometrial cancer (EC). Current clinical guidelines that support using transvaginal ultrasound (TVUS) to screen individuals with postmenopausal bleeding underperform for Black women, who have markedly higher EC mortality. As biopsy-first pathways emerge as a preferred approach, public communication efforts are critical to avoid widening inequity.  Dr. Doll’s team will execute a mixed-methods, community-engaged project via the following specific aims: 1) quantify patient-level risk factors beyond racial identity which most strongly associated with non-diagnostic TVUS within a cohort of nearly 3500 symptomatic Black people; 2) identify the barriers and facilitators to acceptance of a biopsy-first early detection strategy via focus groups with Black women and gender expansive individuals; and use these data to 3) develop and test a culturally tailored public communication toolkit of the novel, but more invasive, biopsy-first approach using community-defined language, priorities, and engagement methods.

Biography

Dr. Kemi Doll completed a bachelor’s degree in biomedical engineering from Duke University, attended medical school at Columbia University, and completed OBGYN residency training at Northwestern Memorial Hospital. Her subspecialty training in gynecologic oncology was completed at University of North Carolina Hospitals, and she has a master’s degree in clinical research from the University of North Carolina School of Public Health where she also completed a post-doctoral fellowship in cancer care quality in the Department of Health Policy and Management. She is a gynecologic oncologist and health services researcher, and is currently an Associate Professor in the Department of Obstetrics and Gynecology at the University of Washington School of Medicine.

Acknowledgement of Support

I am grateful and honored to receive a Victoria’s Secret Global Fund for Women’s Cancers Rising Innovator Research Grant. This award represents an important recognition of the value of health equity research and the urgent challenge of leveraging all we can to improve the diagnosis, treatment, and survival of Black individuals affected by endometrial cancer

Research

Triple negative breast cancer (TNBC) is a difficult to treat breast cancer subtype. Although the introduction of anti-PD1 for treatment of TNBC is an enormous step forward, only a small subgroup of patients benefits from immunotherapy. There is an urgent need to find biomarkers which predict anti-PD1 response in order to select the right patients for this expensive drug and to develop novel immunomodulatory approaches for those patients who do not respond. However, knowledge on how anti-PD1 remodels the tumor microenvironment (TME) in TNBC, which will enable biomarker discovery, is very limited. Using single cell profiling by combining single cell RNA sequencing and complex tissue imaging (MIBI, multiplexed ion beam imaging), the Dr. Kok and her team will determine which immune cells play a crucial role during anti-PD1 response in TNBC patients, either as effector cells or immunosuppressive players, as well as their cell state and exact location relative to the breast cancer cells.

Biography  

Dr. Marleen Kok obtained her PhD (NKI) in 2009 in the field of biomarkers for treatment resistance in breast cancer. Her thesis was awarded best thesis in the field of medicine. She is a medical oncologist and associate professor in translational cancer research at the Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands, where she leads the breast cancer immunotherapy program and a translational breast cancer immunology laboratory. She is working at the forefront of innovative immunotherapy trials. The mission of her clinical and translational team is to improve immunomodulatory treatments for breast cancer patients.

Acknowledgement of Support 

The Victoria’s Secret Global Fund for Women’s Cancers Rising Innovator Grant allows us to investigate cancer-immune interactions in-depth in patients with TNBC in the context of anti-PD1 treatment. This opportunity can form the foundation for both putative predictive tests as well as create novel avenues of immunomodulatory treatment for those patients with TNBC with poor disease outcome.

Research

Dr. Liu and her team will investigate whether targeting replication stress with combined WEE1 and ATR inhibition will have synergistic activity in high-grade endometrial cancer. These cancers are characterized by molecular alterations suggesting high intrinsic replication stress, including alterations in TP53, CCNE1, MYC, and ERBB2. The effect of WEE1 inhibitors and ATR inhibitors on replication stress biomarkers, including pRPA2-S33 and γH2AX, and replication fork dynamics, including replication fork speed and inter-origin distance, will be evaluated in cell lines and patient-derived organoid (PDO) models of high-grade endometrial cancer. The anti-tumor effect of combined WEE1 and ATR inhibition will be further evaluated in cell lines and PDOs utilizing ATP- and imaging-based assays of cell viability. Additionally, evaluation of anti-tumor activity of WEE1 and ATR inhibition will be performed in select patient-derived xenografts. The findings from these studies will provide critical information that could identify a novel active targeted therapy for high-grade endometrial cancers.

Biography

Joyce F. Liu, MD, MPH received her MD from Harvard Medical School and her MPH from the Harvard School of Public Health.  She completed internal medicine residency at Brigham and Women’s Hospital and medical oncology fellowship at Dana Farber Cancer Institute (DFCI).  She is currently an associate professor of medicine at DFCI and Harvard Medical School, where she is a gynecologic medical oncologist. She is also the associate chief and director of clinical research for gynecologic oncology at DFCI and the associate clinical research officer for DFCI. Her research focuses on identifying and validating novel therapies for gynecologic cancers

Acknowledgement of Support

I am extremely humbled and grateful to be a recipient of this grant.  With this support, I am excited to be able to advance our research into how combining these two replication stress-targeting agents could bring an urgently needed new therapy to our patients with high grade endometrial cancer.

Research

Black women and older women of all races are disproportionately dying of breast cancer in the United States. Despite the critical role of immune fitness in cancer control and therapeutic response, immune health evaluation is not part of clinical risk assessment. It is therefore likely that there are missing opportunities for intervention that could eliminate outcome disparities. Dr. McAllister and her team will test a novel hypothesis that declining immune fitness, which would otherwise limit breast cancer progression, contributes to worse outcomes for both older women and Black women. For Black women in particular, they suggest that constant exposure to race-related stresses causes pre-mature immune aging. The objective of her project is to leverage multiparametric immunoprofiling and pre-clinical modeling to define age- and race-specific immune signatures and identify therapeutic strategies for improving anti-tumor immunity. Ultimately, evaluating immune fitness as part of standard risk assessment may improve breast cancer outcomes for all women.

Biography

Dr. McAllister received her undergraduate degree from the University of Michigan and Ph.D. from Washington University School of Medicine. Her pioneering postdoctoral work at the Whitehead Institute opened a new area of research into systemic regulation of breast cancer progression. She is currently associate professor of medicine at Harvard Medical School and in the Hematology Division of Brigham & Women’s Hospital where her group studies the role of immune fitness in breast cancer control and response to therapy. In 2012, Dr. McAllister received the Presidential Early Career Award for Scientists and Engineers from President Obama for her innovative research.

Acknowledgement of Support

My team and I are extremely grateful to the Victoria’s Secret Global Fund for Women’s Cancers, in Partnership with Pelotonia and AACR. The support will enable us to gain critical insights into immune-related determinants that underlie the current disparities in breast cancer outcomes for both older women and Black women.