# Using implantable microdevices for deep phenotyping of multiple drug responses in brain tumor patients

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $682,907

## Abstract

Gliomas are a particularly aggressive type of brain cancer with poor prognosis that affect about 20,000 newly diagnosed
patients in the US annually. There is high interest in identifying predictive biomarkers of response to established
treatments such as Temozolomide, and to identify response and resistance biomarkers for new single and combinations
treatments for gliomas, as there is evidence that an effective adjuvant treatment strategy can improve survival
outcomes for patients. Few tools exist currently to identify such biomarkers and prioritize which agent(s) to administer
to individual patients in order to maximize the impact of drug treatment.
We will conduct a clinical study in which we measure the tumor responses to 20 distinct therapies across a cohort of
32 patients. Using only intrasurgical procedures, implantable microdevices (IMD) are placed into tumors placed into
tumors during already scheduled tumor resections, remain in the patient for the duration of surgery, and are extracted
along with the resected tumor specimen. IMDs enable readouts for each treatment that include immunohistochemical,
transcriptomic, immune and tissue biomarkers, thereby effectively performing 20 biomarker trials at minute drug
exposure levels in each patient with three-fold replicates.
Several key advances will be achieved in this project. First, safety, feasibility and clinical integration of the technical
workflow will be demonstrated in a statistically significant manner. This is key towards establishing broader clinical use
for this technology in the intrasurgical setting. Secondly, we will examine in a retrospective analysis whether the IMD
readout at Temozolomide (TMZ) reservoirs can serve as a predictive marker for standard systemic TMZ treatment
response and progression-free survival at 6 months for each patient. This would constitute a major advance for glioma
patients, as TMZ is the most frequently administered adjuvant treatment in this disease, and the MGMT promoter
methylation status is only a limited predictor of TMZ efficacy for a subset of glioma patients. Third, we will use
multiplexed state-of-the-art deep tissue phenotyping to characterize the biological response of each patient’s tumor
exposed to each of 20 drugs on the microdevice. This will result in a comprehensive catalogue of drug phenotypes for
20 distinct therapies in GBM patients, and we will use this data to systematically identify resistance pathways to
available therapies. In addition, by examining the tumor for genetic and physiologic changes, we can in vivo correlate
existing ‘omic’ biomarkers of tumor response to multiple drugs. This addresses a major knowledge gap in the field, as
such a dataset is not feasible to obtain with traditional systemic clinical trials. The drug phenotyping includes spatial
transcriptomics and metabolomics to identify specific biomarkers in the tumor microenvironment that correlate with
high and low phenotypic response to each therapy. This stud...

## Key facts

- **NIH application ID:** 10891702
- **Project number:** 5R01CA283905-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Oliver Jonas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $682,907
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891702

## Citation

> US National Institutes of Health, RePORTER application 10891702, Using implantable microdevices for deep phenotyping of multiple drug responses in brain tumor patients (5R01CA283905-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10891702. Licensed CC0.

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