# Surrogate biomarkers for assessing changes in pancreatic cancer tumor microenvironment

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $640,316

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is lethal, with a 5-year survival rate of less than 10%. Radical
surgical resection is the only curative option; however, few pancreatic cancer patients have resectable disease
at diagnosis. For a subset of patients with borderline resectable tumors, neoadjuvant therapies can downstage
the disease and enable surgical resection. Protumor characteristics (i.e., hypoxia, high stromal density, high
tissue pressure, and a high number of immunosuppressive cells) reduce the efficacy of neoadjuvant therapies.
Stereotactic body radiation therapy (SBRT) is more effective than traditional radiation therapy for downstaging
PDAC, but not all tumors are responsive. Traditionally, tumor treatment response is evaluated using
anatomical tumor measurements, but this is limited because tumor size often does not correlate with tumor
response. To improve this situation, we will establish a fundamentally new tool to image PDAC tumors to
augment the available diagnostic imaging. We will advance shear modulus (SM) and vascular perfusion (VP)
as surrogate imaging biomarkers for assessing tumor response to neoadjuvant therapies. In a uniquely
beneficial approach for a difficult tumor to characterize, this project will combine pre-surgical, intra-surgical,
and post-resection imaging with in vivo perfusion assessment and ex vivo pathology. Our extensive pre-clinical
results demonstrate that SM and VP are sensitive to changes in protumor characteristics. Therefore, we
hypothesize that SM and VP changes are direct diagnostics of the tumor microenvironment and can be used to
assess therapeutic efficacy and response. To test this, we will combine shear wave elastography (SWE) with
optical fluorescence tomography (OFT) of indocyanine green optical tissue perfusion tracer to evaluate the
interplay between SM and Gemcitabine perfusion for different therapies, providing more comprehensive
information regarding tumor response. We will develop a new hybrid imaging tool to systematically assess how
SM and VP vary during neoadjuvant therapies through two specific aims: In Aim 1, we will perform pre-clinical
studies with three progressive PDAC murine models that have different features that recapitulate human
disease to evaluate how SM and VP relate to (a) stromal density, (b) the number of immunosupportive cells,
and (c) the degree of hypoxia during SBRT, chemotherapy, and chemoradiation therapy. In Aim 2, we will
clinically translate this work. We will compare our interventional SWE and OFT imaging to magnetic resonance
elastography (MRE) and dynamic-contrast-enhanced magnetic resonance imaging to assess tumor
microenvironmental changes during SBRT, chemotherapy, and chemoradiation therapy. We will also perform
SWE on excised PDAC to evaluate how SM and VP relates to tumor microenvironment changes. These new
imaging features are potential surrogate biomarkers, enabling clinicians to recognize whether treatment
succeeds or fails. This practice-ch...

## Key facts

- **NIH application ID:** 10339986
- **Project number:** 1R01EB032337-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Marvin M Doyley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $640,316
- **Award type:** 1
- **Project period:** 2021-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339986

## Citation

> US National Institutes of Health, RePORTER application 10339986, Surrogate biomarkers for assessing changes in pancreatic cancer tumor microenvironment (1R01EB032337-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10339986. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*