# Determination of functional and molecular biomarkers of treatment resistance with multimodal optical spectroscopy

> **NIH NIH R01** · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · 2020 · $419,281

## Abstract

PROJECT SUMMARY
We have made great advances in our ability to treat cancer. However, we still lack the ability to determine which
patients will benefit the most from treatment. In head and neck squamous cell carcinoma (HNSCC), the decision
to treat with radiation and chemotherapy is based on anatomical evaluations of tumor stage and progression. In
addition, treatment response is evaluated several weeks post-completion of therapy. An early determination of
treatment resistance would greatly alleviate the pain and suffering for patients with treatment-resistant tumors
who would otherwise undergo several weeks of ineffective therapy. Three research teams with complementary
expertise in diffuse reflectance spectroscopy, Raman spectroscopy, and radiation biology have joined forces to
develop a non-invasive, quantitative tool that can reveal key metabolic, functional and molecular changes in
response to radiation and chemotherapy in HNSCC. Specifically, this multi-modal optical sensing approach
affords simultaneous, real-time determination of tumor oxygenation and metabolism that play key
complementary roles in shaping treatment resistance. The integration of diffuse reflectance and Raman
spectroscopic modalities is motivated by our preliminary data acquired from radiation-resistant and sensitive
tumor xenografts that shows significantly higher reoxygenation and elevated lipid and glycogen content in the
radiation-resistant tumors. This application seeks to significantly advance these preliminary findings for
comprehensive characterization of radiation and chemotherapeutic responses. Aim 1 is focused on pre-clinical
studies using diffuse reflectance spectroscopy to investigate short-term and long-term reoxygenation kinetics of
chemo and radiation-resistant and sensitive tumors in response to clinical treatment regimens and, in the
process, identify time-dependent thresholds that can reliably predict radiation resistance. In Aim 2, we will
investigate the dynamic changes in tumor metabolism after radiation and chemotherapy using Raman
spectroscopy and correlate these findings with metabolomics to map the key spectral features to molecular
determinants. Finally, in Aim 3, we seek to translate the consolidated panel of spectroscopic markers through a
pilot clinical study in patients with HNSCC who are scheduled for chemoradiation therapy. To determine the
initial sensitivity of our approach in identifying treatment-resistant tumors within the first half of the therapeutic
regimen, we will develop and employ a multimodal inverse spatially offset Raman and diffuse reflectance
spectroscopy probe that is compatible with a standard clinical laryngoscope. Successful completion of these aims
will delineate functional and molecular changes associated with radiation and chemoresistance at unprecedented
time scales. This knowledge of radiobiological changes occurring immediately after therapy will not only aid in
differentiating treatment responders and non-respon...

## Key facts

- **NIH application ID:** 9994864
- **Project number:** 5R01CA238025-02
- **Recipient organization:** UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
- **Principal Investigator:** Narasimhan Rajaram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $419,281
- **Award type:** 5
- **Project period:** 2019-08-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994864

## Citation

> US National Institutes of Health, RePORTER application 9994864, Determination of functional and molecular biomarkers of treatment resistance with multimodal optical spectroscopy (5R01CA238025-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994864. Licensed CC0.

---

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