Leptomeningeal metastasis (LM), or the spread of tumor cells into the cerebrospinal fluid, is an increasingly common complication of cancer that results in rapid neurologic disability and death. Colonization of leptomeningeal space by cancer cells can take years or even decades after primary cancer diagnosis. The molecular basis of this devastating process remains virtually unknown.
In the proposed project, we plan to investigate why some breast cancers become metastatic and lead to LM, how therapy contributes to the dormancy and re-emergence of these cells, and ultimately, which genes are involved in lethal recurrence. Working from our observations from patient samples and unique experimental mouse models, we will dissect the mechanism of cancer cell entry to the spinal fluid using cutting-edge technologies. Moreover, the presence of a functional immune system in our novel syngeneic mouse models enables us to target immune pathways essential for the development of LM. Due to the routine clinical management of breast cancer patients with LM at MSKCC, we have access to a unique collection of fully annotated spinal fluid samples. This gives us the opportunity to validate findings from mouse studies in human disease. We aim to identify molecules that promote the colonization of leptomeninges by breast cancer cells. We will then identify breast cancer patients with high risk of LM development and target these essential genes with FDA-approved and experimental drugs in mice.
Dr. Remsik obtained his Ph.D. in Biology at Masaryk University in the Czech Republic under the supervision of Dr. Karel Soucek. During his graduate studies, Dr. Remsik studied intratumoral heterogeneity in breast and prostate cancer, focusing on the role of epithelial-to-mesenchymal transition on the cell surfaceome. Jan is currently a postdoctoral fellow at the MSKCC’s Human Oncology & Pathogenesis Program in the lab of Dr. Adrienne Boire.