Two WCM Scientists Awarded First-Ever Pershing Square Foundation Ovarian

In a significant advancement for ovarian cancer research, Dr. Juan R. Cubillos-Ruiz and Dr. David Lyden of Weill Cornell Medicine have been named the inaugural recipients of the prestigious 2025 Pershing Square Foundation Ovarian Cancer Challenge Grant. This noteworthy award honors their groundbreaking work in deciphering the complex biology underlying ovarian cancer, with a particular focus on tumor metastasis and immune system interactions within the peritoneal cavity. The grant provides $750,000 in funding over three years, aimed at accelerating innovative approaches to early detection, treatment, and prevention of a malignancy that claims nearly 13,000 lives annually in the United States alone.

Ovarian cancer remains one of the deadliest cancers affecting women worldwide, largely due to late-stage diagnosis and the paucity of effective therapies targeting metastatic disease. Dr. Cubillos-Ruiz brings to this challenge decades of expertise in the immunobiology of ovarian cancer, leveraging his role as the William J. Ledger, M.D. Distinguished Associate Professor of Infection and Immunology in Obstetrics and Gynecology and co-leader of the Cancer Biology Program at the Sandra and Edward Meyer Cancer Center. His team proposes a novel therapeutic paradigm that centers on manipulating a unique subset of immune cells resident within the peritoneal cavity. Unlike conventional approaches that target tumor cells directly, this strategy seeks to educate the immune system to recognize, eliminate, and establish long-term memory against disseminated ovarian tumor cells, thereby reducing relapse rates.

A fascinating component of Dr. Cubillos-Ruiz’s research is the exploration of the peritoneal immune microenvironment—an anatomical niche notoriously implicated in ovarian tumor spread. The peritoneal cavity houses diverse immune populations that have, until now, been relatively underexamined in the context of metastatic progression. By elucidating the signaling pathways and cellular dynamics governing these immune cells, the lab aims to uncover methods to potentiate their antitumor activity. Furthermore, they intend to repurpose immunotherapeutic agents currently being evaluated in clinical trials for other solid tumors, including head, neck, and liver malignancies, adapting these interventions for ovarian cancer patients who remain underserved by existing treatments.

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In parallel, Dr. David Lyden’s research focuses on the biology of extracellular vesicles (EVs)—nano-sized particles secreted by tumor cells that mediate intercellular communication influencing metastatic dissemination. His work is concentrated on profiling the proteomic landscape of EVs derived from ovarian tumors to identify biomarkers predictive of metastatic potential and organotropism, particularly regarding the omentum, a fatty apron-like structure frequently colonized by ovarian cancer cells. By isolating and characterizing the proteins expressed on the surface of these vesicles, Dr. Lyden is developing diagnostic tools capable of detecting ovarian cancer in its earliest stages through a minimally invasive blood test.

The clinical implications of Dr. Lyden’s investigations are profound, as early detection dramatically improves patient prognosis yet remains exceedingly difficult due to the disease’s often silent progression. His team is also dissecting the role of EVs in establishing pre-metastatic niches—specialized microenvironments in distant tissues that facilitate tumor cell engraftment and growth. By understanding the molecular, cellular, and metabolic alterations induced by these vesicles in lymph nodes and omental tissue, researchers aspire to identify novel therapeutic targets to disrupt metastatic seeding before overt secondary tumors develop. This preemptive approach offers a promising horizon for reducing ovarian cancer mortality by intervening at the earliest points of disease dissemination.

The strategic partnership between these two research trajectories underscores a holistic approach to combat ovarian cancer, addressing both immune-based eradication of existing disease and the development of sensitive diagnostics to preempt metastatic spread. Dr. Cubillos-Ruiz highlights the critical timing of this award, citing a concerning decline in federal funding dedicated to ovarian cancer, which has imperiled the advancement of therapeutic innovations in this often-neglected domain. The philanthropic intervention by the Pershing Square Foundation thus represents a vital lifeline, enabling high-risk, high-reward projects that push the boundaries of cancer biology and treatment paradigms.

Reflecting on his journey, Dr. Cubillos-Ruiz noted that the grant builds upon earlier support received through the 2017 Pershing Square Sohn Cancer Research Alliance Award, which provided foundational resources instrumental in expanding his lab’s capabilities and catalyzing seminal discoveries in tumor immunology. The current project’s overarching ambition is to translate basic biological insights into transformative immunotherapies that are both precise and durable, capable of overcoming the notorious resistance of ovarian tumors to existing modalities. This involves decoding the mechanisms by which tumors evade immune surveillance and leveraging these insights to engineer therapeutic vaccines or cellular therapies.

Dr. Lyden’s commentary underscores the unmet need for comprehensive investigation into the metastatic cascade, particularly in the context of ovarian cancer. His research on EV-associated proteins not only aims to refine early diagnostic criteria but also seeks to inform novel interventions that can thwart tumor cell colonization at remote sites. By delineating the biogenesis, cargo, and functional impact of extracellular vesicles, his lab aspires to craft a multifaceted strategy that integrates diagnostics with targeted therapeutics, ultimately improving survival outcomes through earlier and more effective clinical management.

An event slated for later this month in New York City will publicly honor Drs. Cubillos-Ruiz and Lyden alongside other distinguished recipients of the Ovarian Cancer Challenge Grant. This platform will facilitate knowledge exchange and foster collaborations essential for advancing ovarian cancer research. Beyond immediate scientific goals, the award spotlights the critical role philanthropic funding plays in sustaining investigative momentum, particularly for cancers that remain under-recognized and underfunded in national research agendas.

Together, the work led by these prominent investigators epitomizes the intersection of cutting-edge immunology, molecular oncology, and translational science in addressing one of the most formidable cancer challenges. Their efforts hold promise not only for the ovarian cancer community but also for broader applications involving metastatic disease and immune modulation. As the demands for innovation intensify in oncology, the support rendered by visionary funding entities like the Pershing Square Foundation catalyzes breakthroughs that may soon deliver hope to patients worldwide who face daunting prognoses.

The importance of integrating basic and clinical research to confront ovarian cancer’s complexities cannot be overstated. The endeavors of Drs. Cubillos-Ruiz and Lyden demonstrate an inspiring commitment to unraveling the intercellular dialogues, immune evasion tactics, and metastatic mechanisms that define this disease. By bridging fundamental science with potential clinical applications, their research paves the way for a new era of personalized, immune-informed interventions. As this grant-funded research unfolds over the coming years, it remains poised to make transformative contributions to the detection, prevention, and treatment landscape of ovarian cancer.

Subject of Research: Innovative immunobiology and extracellular vesicle profiling to improve ovarian cancer detection, prevention, and treatment.

Article Title: Two Pioneering Scientists Receive Prestigious 2025 Ovarian Cancer Challenge Grant to Revolutionize Diagnosis and Therapy

News Publication Date: May 29, 2025

Web References:

Weill Cornell Medicine news release: https://news.weill.cornell.edu/news/2017/05/four-cancer-researchers-win-funding-to-conduct-high-risk-high-reward-projects
Pershing Square Foundation:

Image Credits: Weill Cornell Medicine

Keywords: ovarian cancer, cancer research, extracellular vesicles, metastasis, immunotherapy, peritoneal cavity, biomarkers, early detection, tumor microenvironment, pre-metastatic niche

Tags: Dr. David LydenDr. Juan R. Cubillos-Ruizearly detection of ovarian cancerfunding for cancer researchimmune system interactionsinnovative therapies for metastatic diseaseovarian cancer researchPershing Square Foundation grantprevention of ovarian cancertreatment strategies for ovarian cancertumor metastasis studywomen’s health and cancer

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