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CSF biomarkers of brain metastases from lung cancer

Institution: University of California, San Francisco
Investigator(s): James Rubenstein, M.D., Ph.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12IT-0246 Award: $100,000
Subject Area: Cancer
Award Type: Inno Dev & Exp Awards (IDEAS)

Initial Award Abstract
Brain metastases represent a major problem in patients with both non-small cell and small cell lung cancer histology. Relapse in the brain occurs in at least 25% of patients with surgically removed non-small cell lung cancer and 65% of patients with small cell lung cancer. Because of this natural propensity for central nervous system (CNS) dissemination, there has been increasing interest in the preventive use of radiation treatment of the brain (prophylactic cranial irradiation) in selected patients who have responded well to surgery, chemotherapy and radiation treatment of their primary tumors. This prophylactic cranial irradiation has been shown to significantly decrease the risk for CNS relapse in the brain, and it may result in the extension of survival. However, because of concerns regarding the toxicities associated with brain irradiation, routine use of this treatment is restricted.

We propose to use state-of-the-art molecular analysis of the cerebrospinal fluid (CSF) in order to identify biomarkers of brain metastases from lung cancer. The identification of such biomarkers would have a significant impact in the treatment of patients with this malignancy. First, CSF biomarkers for lung cancer may help doctors decide which patients need prophylactic cranial irradiation. Second, CSF biomarkers for lung cancer brain metastases could help doctors determine whether a brain tumor is caused by metastatic lung cancer, whether the tumor began in the brain, or whether it metastasized from a different organ besides the lungs. Thus, some neurosurgical procedures might be avoided to reduce risks to patients. Third, CSF biomarkers help doctors evaluate the clinical response. If such biomarkers disappear after treatment, then the doctors would be confident that the tumor cells are absent. Finally, the identification of CSF biomarkers may also be relevant to more early stage lung cancer. Such biomarkers could be used to screen patients who are at risk for lung cancer, so that some patients may achieve early diagnosis and cure before they develop symptoms.

We plan to search for informative and novel CSF markers using combined gene expression profiling and mass spectrometry proteomics approaches. Our preliminary work in gene profiling on lymphomas has yielded promising candidate markers, and we believe that a similar approach in lung cancer patients will provide evidence for “lead” CNS markers for more detailed validation. The proteomics work will be done with a biotech company, SurroMed, Inc. in Mountain View, CA. We hope that our project will lead to better clinical management of brain metastasis. Of the 150,000 new brain metastatic cancers diagnosed yearly, approximately 40,000 originate from lung cancers. This research topic represents an ideal application for the newly emerging gene profiling and proteomics technologies.