Brain tumors are highly complex, individual tumors, which require tailored treatment. However, to this date, therapeutic decision-making for brain tumor patients, such as patient enrollment into distinct clinical trials, is predominantly not based on the individual molecular makeup of a brain tumor disease but rather done by molding patients into risk groups inherently created by imprecise clinical and end-stage morphological measures. Such risk groups ignore the individual molecular fate of each brain tumor disease.
Robust molecular profiling of brain tumors represents a crucial component for the translation of molecular advances in neuro-oncology to tailored clinical practice. By reflecting the individuality of each brain tumor, molecular profiles can expose the presence or absence of distinct disease-associated, biological consistencies in a given tumor that constitute the point of action of molecularly targeted therapies. In addition, the ability of such profiles to estimate individual patient risk represents a major advantage relative to risk grouping of patient populations who share similar clinico-pathologic disease characteristics, which provides only average predictions. Molecular profiles thus lend themselves to assist in difficult clinical decision-making.
Our laboratory is interested in “holistic” (genome-wide) molecular profiling strategies as well as “focused” strategies that utilize innovative and early phase biomarker assays to generate a unique “profile” for a brain tumor disease that provides insights into the prognosis and/or the most appropriate therapeutic regimen for any single patient.
|Holistic analytic approach|
As opposed to other genome-wide profiling efforts, which primarily aim at identifying predictive/ prognostic metagene predictor sets without looking at underlying mechanisms, our approach examines genome-wide profiles through the viewpoint of larger molecular pathways and networks rather than a gene-by-gene basis. Metagene predictors may be important for general prognostic/predictive value, but pathway and network modeling obtains mechanistic insights and can uncover new disease and resistance mechanisms in brain tumors, which is a crucial prerequisite for new molecularly targeted therapies. It can also assess established resistance pathways/networks to predict a patient’s response to contemporary treatment and to guide tailoring treatment based on mechanisms that target critical molecular pathways.
Focused Analytic Approach
Focused target screens complement the holistic approach in that they assess specific members of molecular pathways/networks deemed to critically determine their status at the protein level. For protein analysis, we are utilizing novel assay technology that combines the strengths of both protein recognition and nucleic acid chemistry to result in a technology that is able to detect minute amounts of protein alone or in complex in as few as 10,000 brain tumor cells, easily attainable from a small stereotactic biopsy core. This methodology helps us establishing predictive tests that assist therapy decisions.