Advancing strategies to combat BRCA-linked cancer threats

Two projects, supported by the Gray Foundation, offer hope to individuals with BRCA1 and BRCA2 gene mutations.

By Randy Fox

This microscopic view shows the molecular features of an early ovarian precancer (highlighted in aqua and pink). Image: Santagata lab

In their quest to transform cancer care, two researchers in the Harvard Medical School Laboratory of Systems Pharmacology (LSP) are leading a pair of projects that offer hope to individuals with BRCA1 and BRCA2 gene mutations. These mutations significantly increase the risk of developing breast and ovarian cancers at a young age, prompting some carriers to consider invasive procedures, such as prophylactic mastectomy or oophorectomy (removal of ovaries), even before a cancer diagnosis.

“Developing new diagnostics to assist with challenging decisions about preventive surgery or treatment of early cancers can profoundly affect quality of life,” says Peter Sorger, AB ’84, PhD, the Otto Krayer Professor of Systems Pharmacology in the Blavatnik Institute at HMS.

He and Sandro Santagata, MD, PhD, an associate professor of systems biology at HMS and an associate professor of pathology at Brigham and Women’s Hospital, seek to shift cancer care toward proactive, less invasive strategies.

Building a portal for data-driven, tailored cancer treatments

A central element of their work is the Gray BRCA Pre-Cancer Atlas, a pioneering digital resource for data on early-stage breast and ovarian cancers. (The “Gray” denotes the Gray Foundation, which supports the research of leading physicians and scientists who are focused on the prevention, interception, and early detection of BRCA-related cancers.) Sorger notes that remarkably little information is available about cancers at early, potentially curable stages, emphasizing, “This portal is particularly important because much of the data we are collecting and releasing does not yet have an organized home in an NIH-supported repository.”

These projects align with our mission to address BRCA-related cancer challenges through innovative research, moving us closer to our ambition to stop these cancers before they start.

Dana Zucker

By integrating extensive molecular and imaging data, the portal—a cross-institutional effort—helps scientists and clinicians correlate molecular information with patient outcomes, leading to more personalized treatment approaches. It also fosters global collaborations, giving researchers around the world access to cutting-edge findings essential for guiding new research directions and clinical applications.

Probing the origins of serous ovarian cancer

In parallel with the portal’s development, Santagata and Sorger are investigating how serous ovarian cancer initiates. Using spatial transcriptomics and multiplexed imaging—advanced tissue analysis methods—they’re revealing where genes and proteins are expressed within tissue samples. Integrating these approaches using artificial intelligence and machine learning tools has revealed early disease markers for improved diagnosis and future targets for preventive therapies. This effort has been strengthened through a close partnership with Ronny Drapkin, MD, PhD, a leader in ovarian cancer research who is based at the Basser Center for BRCA at the University of Pennsylvania.

“We recently published a study in Cancer Discovery detailing early immune system changes and cancer causing activities observed in ovarian precancers,” says Santagata, highlighting that treatments effective in advanced cancers might also prevent disease at its earliest stages. He cautions, however, that the threshold for applying these therapies to individuals without advanced disease is understandably very high, underscoring the need for deeper insights into early precancer changes.

Leveraging Gray Foundation support

Recognizing the transformative potential of this work, the Gray Foundation recently awarded these two projects $2 million in combined support, building on a prior commitment of more than $1.2 million. In addition, the foundation granted Alyce Chen, MPH, PhD ’12, scientific program manager for the LSP, nearly $750,000 to develop and deploy the computational and informatic components required to support the Gray BRCA Pre-Cancer Atlas.

“We’re grateful for Peter and Sandro’s leadership of this groundbreaking collaborative effort,” says Dana Zucker, MBA ’95, CEO of the Gray Foundation. “These projects align with our mission to address BRCA-related cancer challenges through innovative research, moving us closer to our ambition to stop these cancers before they start.”

The Gray Foundation has contributed nearly $200 million to leading research institutions for the treatment and prevention of BRCA-related cancers.