# Nanotherapeutics for Synergistic Targeting of Myc in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $356,960

## Abstract

Deregulation of c-Myc (Myc) is implicated in the pathogenesis of various types of cancers and in many cases
contributes to their aggressiveness. There has been enormous interest in developing new cancer therapies
that are targeted at Myc. Several small molecule inhibitors have been reported. However, development of
these compounds has been limited by a number of issues including rapid metabolism, poor bioavailability, or
inability of the drug to reach effective concentrations at tumor sites. Recently, we have also discovered that
inhibition of Myc leads to upregulation of glutamine:fructose-6-phosphate amidotransferase-1 (GFAT-1), the
rate-limiting enzyme in the hexosamine biosynthetic pathway (HBP) in several cancer cell lines. Simultaneous
inhibition of Myc and GFAT-1 results in a drastic increase in the inhibition of the proliferation of tumor cells,
suggesting that upregulation of GFAT-1 may represent another barrier that limits the effectiveness of Myc
inhibition-based therapy. This application is focused on the development of an improved therapeutic strategy
that not only improves the efficiency of delivery to the tumor tissues but also simultaneously blocks Myc and
GFAT-1 activities. This will be achieved via the development of a multifunctional nanocarrier that is highly
effective in codelivery of a small molecule Myc inhibitor, 10058-F4 and GFAT-1 siRNA. Three specific aims will
be pursued in this application. Aim 1 will focus on the development and in vitro characterization of
multifunctional carriers that are effective in co-formulating 10058-F4 and GFAT-1 siRNA. Aim 2 will examine
the pharmacokinetics and biodistribution of both 10058-F4 and GFAT-1 siRNA in tumor-bearing mice. Aim 3
will investigate the in vivo therapeutic effect of codelivery of 10058-F4 and GFAT-1 siRNA via an optimal
nanocarrier. Both human and murine prostate cancer models will be used in this application. Successful
completion of this study may lead to not only the development of a new delivery system but also a new
mechanism-based therapy.

## Key facts

- **NIH application ID:** 9830630
- **Project number:** 5R01CA223788-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Song Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,960
- **Award type:** 5
- **Project period:** 2017-12-05 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830630

## Citation

> US National Institutes of Health, RePORTER application 9830630, Nanotherapeutics for Synergistic Targeting of Myc in Prostate Cancer (5R01CA223788-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830630. Licensed CC0.

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