# Role of tumor heterogeneity on receptor engagement

> **NIH NIH R01** · RENSSELAER POLYTECHNIC INSTITUTE · 2021 · $598,957

## Abstract

Effect of tumor cell heterogeneity on receptor engagement MPIs: Barroso, Corr and Intes
ABSTRACT
Precision medicine in oncology has shown great promise in improving patient prognosis and well-being.
However, current clinical targeted therapies that act on specific molecular targets associated with cancer have
been less effective than anticipated, mainly due to intrinsic and/or relatively rapid acquisition of resistance.
Cellular heterogeneity, in particular tumor/stroma compositional heterogeneity and variations in the expression
of membrane-bound receptors, has been implicated as an important driver of resistance to anti-cancer
treatments. Though, to date, no analytical tool can provide means to replicate these heterogeneities in vitro
and can monitor quantitatively the binding of therapeutic antibodies or drug-antibody conjugates to their
respective targets, which is critical for drug deliver efficacy. Herein, we propose to integrate a biomanufacturing
platform with 3D optical molecular imaging to investigate, for the first time, the influence of tumor cell
heterogeneity, namely compositional heterogeneity as well as receptor level expression heterogeneity (i.e.,
Her2+, EGFR and Tfn), on target-receptor engagement. The unique characteristics of our approach are the
ability to manufacture on demand “histology grade” 3D heterogeneous breast tumor systems and quantify
ligand-receptor engagement in these systems beyond the current depth limits of microscopy. To achieve our
goals, we have assembled a multidisciplinary research team with established expertise and collaboration track
record in all facets on the program. Upon completion of this project, we will have integrated this analytical
platform to assess receptor engagement of well-known drug carriers in heterogeneous 3D cancer systems.
This platform is expected to advance personalized medicine by providing tools and approaches that can be
used to critically assess tailored therapy management strategies.

## Key facts

- **NIH application ID:** 10132999
- **Project number:** 5R01CA207725-05
- **Recipient organization:** RENSSELAER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Margarida Barroso
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $598,957
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132999

## Citation

> US National Institutes of Health, RePORTER application 10132999, Role of tumor heterogeneity on receptor engagement (5R01CA207725-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132999. Licensed CC0.

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