On-Chip Characterization of Brain Tumor Heterogeneity by Single Cell Mass Spectrometry

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Despite the arsenal of developed and FDA-approved anti-cancer drugs, cancer is still a leading cause of death. The limiting factor in treating cancers is no longer solely drug availability, but now also includes the need for more comprehensive diagnostic approaches. Biochemical factors that cause tumors to develop and progress vary from one cancer to another, as well as from one patient to another. Personalized cancer care requires treatment that specifically targets biomolecules defining a given tumor, based on knowledge of the tumor’s molecular features.

The World Health Organization recognizes more than 125 types of brain tumors. Glial tumors account for 40% of all intracranial tumors. The most malignant form, glioblastoma multiforme (GBM) still resists elaborate treatment with a median survival of 12–15 months. Nevertheless, there is wide variation in survival with some patients responding well to treatment while others do not. In order to extend survival and improve quality of life for patients with GBM, it is necessary to choose the most effective treatment. Characterizing the individual molecular characteristics of a patient’s tumor can inform treatment selection and optimize outcomes.

Unfortunately, brain tumors are heterogeneous and consist of populations of cells with different degrees of tumor initiating potential, and different susceptibility to treatment. The isolation and characterization of tumor stem cells in samples of human brain tumor tissue have been limited in terms of clinical translation due to the intensive labor involved in each specimen analysis.

The project team proposed an approach that uses microfabricated devices for single cell culture and analysis of brain tumor cells. The technology could help identify and implement clinical markers that correlate with the effectiveness of a treatment. This project will leverage the collaborative expertise of three groups in the areas of mass spectrometry and neuroscience (Nathalie Agar, BWH, principal investigator), genetics and computational biology (Philip De Jager, MD, BWH, co-principal investigator), and single-cell bioanalytical engineering (Christopher Love, PhD, MIT, co-principal investigator).