# Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers

> **NIH NIH U2C** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $1,723,236

## Abstract

ABSTRACT - Overall
We propose to create an Omic and Multidimensional Spatial (OMS) Atlas that will enable discovery of
mechanisms of resistance that arise in individual patients with metastatic breast and prostate cancer during
treatment with current generation targeted therapeutic combinations and immune checkpoint inhibitors. The
OMS Atlas is motivated by the fact that these treatments typically are only transiently effective in the metastatic
setting. Possible resistance mechanisms may be intrinsic to the tumor cells or derive from the diverse
microenvironments in which the tumor cells live. The OMS Atlas will focus on elucidating these resistance
mechanisms in three specific current generation clinical scenarios: (a) hormone-receptor positive breast cancer
(HRBC) undergoing treatment with a CDK4/6 inhibitor in combination with endocrine therapy, (b) triple negative
breast cancer (TNBC) undergoing treatment with a PARP inhibitor and an immunomodulatory agent, and (c)
castration resistance prostate cancer (CRPC) undergoing treatment with enzalutamide. We will accomplish this
through work in four areas. A Biospecimen Unit will prospectively collect, manage, and distribute longitudinal
clinical information, blood, and biopsies from 20 patients from each of two metastatic breast cancer cohorts and
one prostate cancer cohort that will be analyzed to create three OMS Atlases. The biopsies will be preserved to
enable analyses using multiple characterization modalities. A Characterization Unit will analyze (a) OCT frozen
specimens using Topographic Single Cell Sequencing (TSCS) and Single-cell Combinatorial Indexing ATAC-
seq (sci-ATAC-seq) to elucidate spatially defined genomic changes and chromatin accessibility in single cells,
(b) formalin fixed, paraffin embedded (FFPE) specimens using multiplex immunohistochemistry (mIHC) to
assess the immune microenvironment and cyclic Immunofluorescence (cycIF) to assess the composition and
molecular states of tumor cells and their microenvironments, and (c) paraformaldehyde fixed, resin embedded
(PFRE) specimens using a Focused Ion Beam Scanning Electron Microscope (FIB-SEM) to identify
ultrastructural changes in 2D images and targeted 3D images with 4-nm resolution. Omic characterization of the
same tumor samples will be provided by the SMMART Program. A Data Analysis Unit will develop and deploy
tools to (a) manage, analyze, and visualize Tier 1 data comprised of raw sequence data and images to generate
unimodal Tier 2 results, (b) integrate omics and imaging data through crosswise mapping to create single
timepoint tumor maps and quantify systems biological functions of tumor cellular subpopulations to generate Tier
3 results, and (c) explore differences between pre- and on/post-treatment tumor maps to reveal mechanisms of
resistance that comprise Tier 4 results. We will collaborate with private sector partners to evaluate and adopt
next generation technologies that increase analytical power and speed and ...

## Key facts

- **NIH application ID:** 10246885
- **Project number:** 5U2CCA233280-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jeremy Goecks
- **Activity code:** U2C (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,723,236
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246885

## Citation

> US National Institutes of Health, RePORTER application 10246885, Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers (5U2CCA233280-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246885. Licensed CC0.

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