# Development of a novel biochemical tool with tumor-selective theranostic anti-cancer potential

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $185,247

## Abstract

Project Summary
Cancer remains one of the deadliest diseases in the world. In the United States alone, it is projected that an
estimated 1,762,450 new cases of cancer will be diagnosed and about 606,880 people are projected to die
from this disease by the end of 2019. While cancer patients have many treatment options, the lack of effective
and tumor-selective treatment strategy remains a major obstacle in the fight against cancer today. Undesirable
toxicities due to the development of resistance to a single drug when given at high doses, especially to the
wrong patients can cause harmful side effects triggered by unintended damage to normal cells. Most
chemotherapies that are still commonly used in the clinic for cancer treatment are DNA-targeting agents (e.g.,
crosslinking drugs), which inhibit aberrant replication and transcription in tumors to induce cell death.
However, these agents also affect normal tissues. Therefore, we developed a new class of DNA crosslinking
agent that utilizes the unique properties of cancer versus normal cells for tumor-selective activation. Here, we
propose to investigate the tumor-selective therapeutic effects of our prodrug that is preferentially activated to
induce lethal DNA damage only in tumors due to characteristically higher hydrogen peroxide (H2O2) levels
needed for drug activation; whereas normal cells are protected due to higher Catalase expression that
quenches H2O2. We will also identify reliable predictive biomarkers in tumors to possibly stratify patients who
will significantly benefit from our innovative treatment approach compared to non-tumor-selective crosslinking
agents used in the clinic (e.g., chlorambucil). Our promising lead compound will then be rationally improved to
have a “theranostic” application (a molecule with both therapeutic and diagnostic capabilities) to potentially
measure therapeutic response immediately following treatment for dose optimization. Our other objective is to
examine whether combinatorial strategies involving our novel agents and genetic/pharmacological alterations
of critical factors involved in H2O2 production and DNA repair may cause additive or synergistic lethality. In this
aim, we will develop a precision-guided treatment strategy to sensitize the tumor-selective therapeutic effects
of our new anti-cancer drugs as a monotherapy or combined with existing agents (at low doses) that are known
to generate H2O2 preferentially in tumors to enhance the killing effect of our H2O2-activatable DNA crosslinking
agent. Our mechanistic and therapeutic response studies will be done using normal and malignant cancer
models, particularly in lung cancer, which still remains the leading cause of all cancer-related deaths. If our
initial hypothesis is correct, our new anti-cancer drug and treatment strategy based on predictive cancer
biomarkers could accurately identify patients with malignant cancers that will most likely respond to the
treatment, reduce life-threatening side-e...

## Key facts

- **NIH application ID:** 10246511
- **Project number:** 5R21CA253645-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Edward Ayson Motea
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,247
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246511

## Citation

> US National Institutes of Health, RePORTER application 10246511, Development of a novel biochemical tool with tumor-selective theranostic anti-cancer potential (5R21CA253645-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246511. Licensed CC0.

---

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