Weill Cornell Medicine received a $2.5 million, three-year grant from the Department of Defense on July 16, 2026, to develop new therapies with fewer side effects for triple-negative breast cancer. The funding, awarded through the Department of Defense Breast Cancer Research Program Breakthrough Award, supports the creation of first-in-class drugs targeting a protein called UBR5 that is frequently overproduced in aggressive breast cancers.

The project is led by co-principal investigators Xiaojing Ma, a professor of microbiology and immunology and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and Gang Lin, a professor of research in microbiology and immunology and a medicinal chemist at the same institution. Together, they aim to translate years of foundational research into therapeutic candidates that could fill a critical gap in treatment options for a form of breast cancer that currently lacks effective targeted therapies.

Triple-negative breast cancer is defined by the absence of three key proteins—estrogen receptor, progesterone receptor, and HER2—that are the targets of many existing breast cancer treatments. Because it lacks these markers, patients with this subtype are often limited to chemotherapy as their primary treatment option, which can cause significant side effects and may not prevent recurrence or metastasis. The new research seeks to address this unmet need by focusing on UBR5, a protein that many tumors produce at substantially higher levels than most normal tissues.

In healthy cells, UBR5 helps regulate the activity and turnover of proteins involved in cell growth, DNA repair, and the tagging of damaged or faulty proteins for disposal. However, many cancers hijack UBR5 to promote tumor growth, spread, and resistance to immune attack. Previous work from Ma’s lab, published in 2017, showed that genetically disrupting the UBR5 gene in preclinical models slowed breast tumor growth and reduced the ability of cancer cells to metastasize to other organs. Those findings provided evidence that UBR5 is functionally required for both tumor growth and metastasis, establishing it as a compelling therapeutic target.

Under the new grant, the researchers are developing two distinct types of therapeutic approaches. First, they will design small molecule drugs that block UBR5’s activity. Second, they will develop protein degraders that direct the cell’s natural waste-disposal system to destroy harmful proteins, including UBR5 itself.

Both strategies aim to interfere with multiple cancer-promoting mechanisms simultaneously—a potential advantage over single-pathway inhibitors. The researchers anticipate these therapies will selectively target cancer cells while reducing side effects, leveraging the fact that UBR5 is overproduced in tumors but present at lower levels in most healthy tissues.

So far, the researchers’ labs have uncovered several compounds that inhibit UBR5, but only at high concentrations. “The potency is not ideal yet; achieving an effective dose on-target requires high concentrations that may induce side effects,” Gang Lin said. He added, “This grant will help us tweak the structures of the inhibitors to make them effective at much lower concentrations.” Lin also noted that a major goal of the project is optimization: “A big win will be optimizing these drug candidates and generating the data needed to move into the next phase of development.”

The team will evaluate how well the drugs work against breast cancer in laboratory models that closely mimic human cancers. This step is critical to determining whether the compounds can advance toward clinical testing. While the current project focuses specifically on triple-negative breast cancer, the implications could extend far beyond this single disease.

“Although the current project focuses on triple-negative breast cancer, UBR5 is also overproduced in ovarian, pancreatic and prostate cancers,” Xiaojing Ma said. She added, “We believe the UBR5 protein is an entirely new vulnerability in these tumors, and this award provides an opportunity to translate years of basic discovery into therapies that could ultimately benefit patients.” Ma also stated, “Success in this program could open the door to a new generation of targeted therapies for multiple aggressive cancers.”

Triple-negative breast cancer accounts for 10 to 15 percent of all breast cancer cases in the United States and is associated with poorer outcomes due to the lack of approved targeted treatments. The development of UBR5-targeted therapies represents a potential paradigm shift, offering a precision medicine approach where none currently exists. Because UBR5 is also overexpressed in other difficult-to-treat malignancies—including ovarian, pancreatic, and prostate cancers—the research could have broad applicability across oncology.

The Department of Defense Breast Cancer Research Program has a long history of funding high-impact, innovative projects that address critical gaps in breast cancer care. By supporting early-stage therapeutic development, this grant enables Weill Cornell Medicine researchers to bridge the gap between basic science and clinical application. If successful, the project could generate the preclinical data necessary to launch formal drug development efforts, bringing new hope to patients with limited treatment options.