The Koschmann lab is studying the molecular mechanisms by which mutations in pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG) can be therapeutically targeted. The Koschmann Lab’s work in precision medicine pushes the boundaries of targeted therapies and precision diagnostics for children diagnosed with these brain tumors. Through highly collaborative basic, translational, and clinical research, the Koschmann Lab strives towards improving outcomes and providing hope for children fighting these devastating diseases.
Correlate CSF and PLasma tDNA Tracking in DMG and DIPG
The Koschmann lab is applying a novel precision medicine approach accounting for both unique tumor biology and optimization of blood brain barrier penetration. We are performing correlate biology work on ongoing precision medicine trials for children and young adults with brain tumors at the University of Michigan, including correlation of spinal fluid analysis with surveillance MRIs.
Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma
We reported (Cantor et al Neuro Oncology. 2022,) the first demonstrated feasibility for serial CSF collection in a prospective high-grade glioma clinical trial. Nonrecurrent patients (those enrolled after initial radiation) with a decrease in CSF H3.3K27M variant allele fraction (VAF) displayed a doubling of time to progression. “Spikes” in cf-tDNA VAF (increase of at least 25%) preceded progression in many cases. In individual cases, patterns of change in VAF over time demonstrate additional clinical utility in terms of differentiating pseudo-progression and bevacizumab (“pseudo-response”) effect. These findings represent a new direction for understanding the feasibility and utility of H3K27M cf-tDNA as a clinically relevant prognostic marker.
Spinal fluid for the diagnosis and treatment monitoring of precision medicine therapies:
Obtaining a tissue sample from children with DIPG and other “midline” high-risk tumors carries significant risk as neurological injury can occur as a result of biopsies. With the aid of the cutting-edge technology, we are developing a new method to instead test a tumor’s growth markers through cerebrospinal fluid (CSF) and blood samples. A safer and less invasive method, this method provides faster recovery and more accurate monitoring of children with high-risk pediatric brain tumors and their responses to targeted therapies. Increasingly, Dr Koschmann and his team are including spinal fluid analysis with surveillance MRIs for children on targeted therapies, including multiple clinical trials active at the University of Michigan. Ongoing work in the Koschmann lab is looking at the DNA and RNA landscape of spinal fluid to uncover new metrics for diagnosis, prognosis and therapeutic response.
