Medical Research

Memorial Sloan-Kettering Cancer Center

Adrienne Boire, Christine Iacobuzio-Donahue, Dana Pe’er
New York, NY
$1,000,000
December 2019

Spread of cancer cells into the spinal fluid, or leptomeningeal metastasis (LM), is an increasingly common complication of cancer that results in rapid neurologic disability and death.  The molecular mechanisms that underlie cancer cell entry into this space remain poorly understood.  Preliminary data from both patient samples and mouse models suggest that certain cancer cells exploit the immune system to gain characteristics that enables them to live and grow in the spinal fluid, which is nutritionally sparse with limited oxygen, protein, glucose, lipids, and micronutrients essential for cell growth.  A team of three investigators at Memorial Sloan-Kettering Cancer Center plans to determine the mechanisms by which cancer cells become able to survive and grow within the spinal fluid environment.  The team hypothesizes that circulating cancer cells enter a structure called the choroid plexus.  Once in this structure, immune cells kill many cancer cells, but certain cells survive this selection, follow immune cells into the spinal fluid and live within this unfavorable environment.  To study these processes, the team proposes to subject patient spinal fluid samples and tissues to advanced analytical techniques to generate an LM “atlas” that describes molecular characteristics of cancer cells capable of living within the spinal fluid.  They will also employ their established mouse models of LM to further investigate the molecular characteristics of these populations of cancer cells.  This translational approach will improve understanding of the essential steps that govern cancer and immune cell entry into the spinal fluid and could provide new insights into therapeutic approaches for cancer metastasis.

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