MetroHealth Scientist Awarded $3.3 Million NIH Grant to Study How Breast Cancer Spreads

MetroHealth Research Institute scientist Khalid Sossey-Alaoui, PhD, has been awarded a five-year, $3.3 million grant from the National Institutes of Health (NIH) to lead groundbreaking research aimed at understanding and preventing the spread of breast cancer.

As principal investigator, Dr. Sossey-Alaoui will lead a first-of-its-kind, multi-institutional and multidisciplinary study focused on how breast cancer cells communicate with and alter distant organs in ways that help cancer spread to other parts of the body – a process known as metastasis.

Breast cancer remains the second leading cause of cancer-related death among women, largely because of its ability to spread beyond the original tumor site.

“Breast cancer becomes much more difficult to treat once it spreads, yet we still do not fully understand how that happens,” said Dr. Sossey-Alaoui, who is also a Professor in the Case Western Reserve University School of Medicine. “This research will help us better understand how breast cancer spreads and could lead to new ways to prevent or treat metastatic disease.”

The project centers on small extracellular vesicles (sEVs) – microscopic particles released by breast cancer cells that carry molecules throughout the body. These vesicles can help prepare distant organs for tumor growth and spread. Dr. Sossey-Alaoui and his collaborators have identified a protein known as Kindlin-2 (K2) as a potential key driver of this process. K2 is found both within cancer cells and inside sEVs, where it may support cancer cell survival, spread and interactions with other cells.

The research team aims to determine how K2-containing vesicles contribute to metastasis and whether disrupting their activity could slow or prevent the spread of cancer. In particular, the study will:

• Examine how K2-containing vesicles promote tumor growth and metastasis using laboratory models and patient-derived tumor samples.
• Test a novel therapeutic approach designed to block the movement of vesicle contents into the cell nucleus, where they can influence gene activity associated with cancer progression.
• Investigate how these vesicles interact with tissues and the immune system and identify the molecular changes they trigger.

The findings could provide new insights into the mechanisms that drive breast cancer metastasis and help pave the way for more effective strategies to prevent and treat advanced disease.

The project is a collaborative effort involving researchers from multiple institutions. Co-principal investigators are Aurelio Lorico, MD, PhD, of Touro University Nevada, and Lucia Languino, PhD, of Thomas Jefferson University. Co-investigators include Amar Desai, MD, PhD, of the Case Comprehensive Cancer Center, and Dan Cai, PhD, of MetroHealth.