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Brain Metastasis Research

by John M. Kirkwood, MD

Professor and Vice Chairman, Department of Medicine
University of Pittsburgh School of Medicine
Director, Melanoma and Skin Cancer Program, UPCI
Hillman Cancer Center


More than half of patients with primary melanoma of the skin that has spread beyond regional lymph glands are at risk of metastasis to the brain, through the blood vessels. The treatment of brain metastases from melanoma has been an obstacle to melanoma therapy that has eluded systemic treatments more than perhaps any other aspect of this disease. Surgery, radiation therapy, and more recently, stereotactically guided radiosurgery have had an increasing role in controlling the symptoms from brain metastases, especially in patients with limited size and number of metastases. Unfortunately, there is no evidence that any treatment prolongs survival in patients with brain metastases.


The International Melanoma Working Group (IMWG) is an international collaboration of leading investigators from multiple disciplines of dermatology, surgery, medicine, and the basic sciences of immunology and molecular biology relevant to this disease. The IMWG mission is to conquer melanoma, and has early taken on the challenge of brain metastasis.


To make progress in our therapy of brain metastasis from melanoma, we must understand the differences between melanoma in the skin where it arises in most patients and in the lymph nodes where spread is first commonly identified, in comparison to the disease when it spreads by the blood stream to the brain, where it is often fatal. Analyzing the tissue, from metastases to the brain in comparison to lymph gland metastases and primary melanoma, will allow us to establish what differences are found in brain metastases using robust new techniques for the ‘high-throughput' characterization of genetic, as well as protein and other aspects of the tumor tissue. It may also demonstrate differences in the immune response and other factors of the patient that may lead to the development of more effective treatments, as well as strategies to prevent the metastasis.


It will take a unique worldwide collaboration to acquire and to appropriately study this tissue. The IMWG provides that capability now.

We are at a crossroads in melanoma therapy with multiple new emerging treatments that ‘target' processes that are components of the drive train for melanoma, as well as multiple new and established treatments that strengthen the immune response and host resistance to melanoma. A concerted approach to brain metastasis is critical to all of these.