# MIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors

> **NIH NIH U54** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $1,990,625

## Abstract

OVERALL – SUMMARY
The selection of relevant therapeutic agents with optimal pharmacokinetic and pharmacodynamic properties to
adequately suppress the intended target across the entire target cell population will be central to the success
of genomics-guided precision medicine strategies. Optimal drug therapy for brain tumors is especially
challenging due to multiple physical barriers within the vasculature and tumor microenvironment that can result
in highly heterogeneous drug delivery. This results in a significant fraction of tumor cells being exposed to sub-
therapeutic drug levels that limit the efficacy of therapy and may lead to compensatory cell signaling and
emergence of drug resistance. Thus, a central tenet of this proposal is that failure to understand limitations in
the physical delivery and distribution of novel therapeutics into brain tumors is a major reason for the collective
failure to extend the exciting treatment advances and survival gains realized in peripheral malignancies to the
treatment of brain tumors. In this PS-OC, we will focus on understanding physical factors that influence
heterogeneous drug distribution and the resulting biology in a highly integrated analysis of patient and animal
tumor models using 3-dimensional MR imaging, stimulated Raman scattering (SRS) microscopy, matrix
assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), immunohistochemistry (IHC),
phosphoproteomics, proximity ligation assays (PLA), and RNAseq. Integration of these data sets across a
series of drugs evaluated in multiple tumor models will elaborate critical factors that modulate distribution of
these drugs and provide the platform for construction of a multi-scale model that could be used to select a
targeted therapeutic with an optimal predicted drug distribution based on MRI features of an individual tumor.
In this context, we will directly meet the goal of the Physical Sciences in Oncology Program to integrate
physical sciences and cancer research perspectives and approaches to address a complex and challenging
question in cancer research. Specifically paraphrased from PAR-14-49, we will address:
Physical Dynamics of Cancer: How do physical properties and forces within tumors, disseminating cells, and
 sites of colonization and metastasis contribute to therapeutic delivery and efficacy? How do these factors
 affect cancer progression and evolution of therapeutic resistance?
Spatio-Temporal Organization and Information Transfer in Cancer: Can the evolutionary dynamics of
 therapeutic resistance be examined in the context of dynamic spatio-temporal environments to better
 define mechanisms of progression and resistance and rationally design therapeutic strategies?

## Key facts

- **NIH application ID:** 9994234
- **Project number:** 5U54CA210180-05
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Jann N. Sarkaria
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,990,625
- **Award type:** 5
- **Project period:** 2016-08-29 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994234

## Citation

> US National Institutes of Health, RePORTER application 9994234, MIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors (5U54CA210180-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9994234. Licensed CC0.

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