# Intratumor heterogeneity and therapeutic resistance

> **NIH NIH R00** · SCRIPPS FLORIDA · 2020 · $104,902

## Abstract

PROJECT SUMMARY
Glioblastoma is one of the most heterogeneous and most aggressive human tumors. It remains an unmet
clinical need, as limited benefits were observed both with targeted treatment and immunotherapy approaches.
We hypothesize that significant variation in tumor microenvironments, generating differences in oxygen and
nutrient supply between these areas, may contribute to survival of specific cancer cell subpopulations. By
developing new in situ applications, suited for formalin-fixed archival specimen, we will retain the relative
localization of cells with distinct genomic features within the tissue sections. Spatial analysis could infer
preferences for particular neighborhoods or niches and cellular interactions. Our proposal will overcome several
limitations of currently available methods, to allow identification of non-hotspot mutations at the single cell level
in situ and simultaneously profile the tumor microenvironment. In Aim 1, we will use two different approaches to
develop an assay that will mark cells with mutations relevant to therapy response in standard intact biopsy
sample. Our new methods will yield a “yes-no” binary result for presence of any, including non-hotspot, mutations
within a genomic region of interest, at single cell level in situ. Thus, they could facilitate screening for actionable
mutations in pathology units, with minimal required equipment and streamlined analysis pipeline. By analyzing
genetically heterogeneous cellular localizations we may identify direct interactions between diverse populations
of cancer cells. To complement this approach, in Aim 2 we will adapt our previously published method, to not
only account for genetically defined populations of cancer cells, but to include markers of normal cells, such as
leukocytes, glial cells and neurons, that all contribute to development of a complex tumor ecosystem. The
proposed projects would complement the parental grant by expanding our methodological capabilities to better
characterize the relationship between heterogeneity and glioblastoma progression.

## Key facts

- **NIH application ID:** 10135438
- **Project number:** 3R00CA201606-05S1
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Michalina Janiszewska
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $104,902
- **Award type:** 3
- **Project period:** 2018-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135438

## Citation

> US National Institutes of Health, RePORTER application 10135438, Intratumor heterogeneity and therapeutic resistance (3R00CA201606-05S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10135438. Licensed CC0.

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