Treating Brain Cancer by Disrupting Cancer Cells' Iron Acquisition Mechanism in Cerebrospinal Fluid


Treating Brain Cancer by Disrupting Cancer Cells' Iron Acquisition Mechanism in Cerebrospinal Fluid


Now available for exclusive licensing

An Innovative Discovery from MSK Researchers

Cancer cells inhabiting the spinal fluid-filled leptomeningeal space face substantial microenvironmental challenges, including limited iron supply within the cerebrospinal fluid (CSF). MSK researchers found that the cancer cells rely on a high affinity iron binding protein, lipocalin-2 (LCN2), to capture sparse iron to support their growth and impair anti-cancer macrophage function.

Significant Clinical Implications

MSK researchers generated remarkable in vivo data in mouse models based on this discovery. Studies have shown that LCN2 is upregulated in response to inflammatory cytokines present in leptomeningeal metastasis (LM).  This mechanism supports growth of cancer cells in their hypoxic microenvironmental niche, and it is required to facilitate iron to support cancer cell growth. MSK investigators have translated this discovery into an innovative clinical approach, and a Phase 1 trial is ongoing to investigate use of an existing iron chelator to interrupt the iron acquisition system used by cancer cells.

There are  additional development opportunities to exploit this vulnerability by blocking the LCN2/SLC22A17 iron acquisition system using antibody or small molecule inhibitors LCN2 or SLC22A17 in the treatment of LM or prevention of cancers likely to progress to LM.

Promising Results to Date

  • Strong animal data demonstrate a critical role of LCN2-signaling axis in cancer cell growth and provide insight into the mechanisms responsible for such activity.
  • An ongoing Phase 1a/1b trial at MSK, “A study of deferoxamine (DFO) in people with leptomeningeal metastasis,” (NCT05184816)” is testing intrathecal delivery of deferoxamine (DFO) for the treatment of leptomeningeal metastasis from solid tumor cancers.
    • Deferoxamine (DFO) is a potent iron chelator, and intrathecal (IT) administration offers the benefit of direct on-site activity while limiting potential for off-site toxicity.
    • DFO has been extensively studied in the clinic and is off-patent.

Healthcare Problem We’re Addressing

Brain metastasis is an area of high unmet need, with incidence in the U.S. estimated as high as 200K per year. LM or spread of systemic cancer into leptomeningeal space is poorly understood and overall survival for patients is often a matter of months. There is currently no effective treatment for LM, with all current treatments considered palliative. This innovation has the potential to provide a novel, effective treatment option for patients with LM.


PCT/US2021/041828, Methods of treating leptomeningeal metastasis, filed July 15, 2021; U.S. National pending


Adrienne Ann Boire, MD, Associate Attending, Neurology, Memorial Hospital, MSK

For licensing/info, contact:  Zariel Johnson, PhD, Licensing Manager, MSK, [email protected]

Stage of Development

Clinical development