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Delivery of chemotherapy and antibodies across the blood–brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the eleventh annual blood–brain barrier consortium meeting

  • Clinical Study-Patient Studies
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Abstract

Although knowledge of molecular biology and cellular physiology has advanced at a rapid pace, much remains to be learned about delivering chemotherapy and antibodies across the blood–brain barrier (BBB) for the diagnosis and treatment of central nervous system (CNS) disease. A meeting, partially funded by an NIH R13 grant, was convened to discuss the state of the science, current knowledge gaps, and future directions in the delivery of drugs and proteins to the CNS, for the treatment of primary and metastatic brain tumors. Meeting topics included CNS metastases and the BBB, and chemoprotection and chemoenhancement in CNS disorders. The discussions regarding CNS metastases generated possibilities of chemoprotection as a means not only to decrease treatment-related toxicity but also to increase chemotherapy dose intensity. The increasing incidence of sanctuary brain metastasis from breast cancer, in part due to the difficulty of monoclonal antibodies (mAbs) such as herceptin to cross the BBB, was one of the most salient “take home” messages of the meeting.

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Acknowledgments

This meeting was supported by the National Institutes of Health grant (R13 CA 86959-05) through the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders.

We thank Aimee Mackillop, Nan Hedrick, Lisa Bennett, Charity Saul and Aliana Kim for coordinating the meeting, and the following for their presentations and for participating in the CNS metastases and chemoprotection discussions: Nancee Albright, Robert Albright, Lily Angelov, Nicholas Avgeropoulos, Gene Barnett, Sue Bell, Lisa Bennett, Susan Blaney, Archie Bleyer, Penelope Brock, Patti Bruns, Joseph Bubalo, Kathleen Campbell, Jonathan Carlson, Patricia Caviness, Gregory Christoforidis, Megan Daman, Tom Dickey, Amy Donahue, Nancy Doolittle, Sandy Ference, David Fortin, Joseph Frank, Kathy Gilliland, Kristy Gilmer-Knight, Jane Gordon, Mary Kay Gumerlock, Paul Gumerlock, Walter Hall, Marianne Haluska, Nan Hedrick, Maria Hopple, Paula Jacobs, Tom Jacobs, Dale Kraemer, Outi Kuittinen, Cynthia Lacy, William Leenders, Manfred Lindau, Paul Lockman, A.B. Madhnakumar, Sadhan Majumder, Sandor Manninger, Diana Manninger-Solymosi, Lazlo Marik, Nathan McDannold, John McGregor, Margaret McMahon, Leslie Muldoon, Gary Nesbit, Edward Neuwelt, H. Stacy Nicholson, Alfred Nuttall, Brian O’Neill, Michael Pagel, Diane Palmieri, Joe Pancrazio, William Pardridge, David Peereboom, Darryl Peterson, Brad Pollock, Marie-Eve Potvin, Stephen Rayhill, Kelly Reavis, Rae Rosenberg, Axel Rosengart, Chloe Sandquist, Edna Shalom, Tali Siegal, Quentin Smith, Lisa Sorenson, Carole Soussain, Alexander Spence, Glen Stevens, Paul Tratnyek, John Trusheim, Rose Marie Tyson, Kishena Wadhwani, Shannan Walker-Rosenfeld, Roy Wu, Jeffrey Wu, Byron Young, Carol Saunders Young.

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Authors and Affiliations

  1. Department of Neurology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road-L603, Portland, OR, 97239-3098, USA

    Nancy D. Doolittle, D. Thomas Dickey, Leslie L. Muldoon, Quentin Smith, Rose Marie Tyson & Edward A. Neuwelt

  2. Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, R35, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    David M. Peereboom

  3. Department of Radiology, The Ohio State University Medical Center, Columbus, OH, 43210, USA

    Gregory A. Christoforidis

  4. Department of Neurosurgery, University of Minnesota, MMC #96, D 429 Mayo Memorial Bldg. 420 Delaware Street, SE, Minneapolis, MN, 55455, USA

    Walter A. Hall

  5. Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Bethesda, MD, 20892, USA

    Diane Palmieri

  6. NHS Trust and the Middlesex Hospital, UCLH NHS Trust, Great Ormond Street Hospital for Children, London, England

    Penelope R. Brock

  7. School of Medicine, Southern Illinois University, Springfield, IL, 62794-9629, USA

    Kathleen C. M. Campbell

  8. Department of Neurology, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA

    Brian Patrick O’Neill

  9. Dept. of Physiology and Biophysics, The Chicago Medical School, North Chicago, IL, 60064, USA

    Darryl R. Peterson

  10. University of Texas, 7703 Floyd Curl Avenue, Mail Code 7933, San Antonio, TX, 78229, USA

    Brad Pollock

  11. Department of Pharmaceutical Sciences, Texas Tech, 1300 Coulter, Amarillo, TX, 79106, USA

    Carole Soussain

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  1. Nancy D. Doolittle
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  2. David M. Peereboom
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  3. Gregory A. Christoforidis
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  14. Quentin Smith
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  15. Rose Marie Tyson
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  16. Edward A. Neuwelt
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Correspondence to Edward A. Neuwelt.

Additional information

OHSU, Portland Veterans Affairs Medical Center (PVAMC) and the Department of Veterans Affairs have a significant financial interest in Adherex, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest was reviewed and managed by the OHSU Integrity Program Oversight Council and the PVAMC Conflict of Interest in Research Committee.

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Doolittle, N.D., Peereboom, D.M., Christoforidis, G.A. et al. Delivery of chemotherapy and antibodies across the blood–brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the eleventh annual blood–brain barrier consortium meeting. J Neurooncol 81, 81–91 (2007). https://doi.org/10.1007/s11060-006-9209-y

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