# Leveraging the GTP Biosynthetic Pathway for Anti-Tumor Therapies

> **NIH CA R37** · ROSWELL PARK CANCER INSTITUTE CORP · 2026 · $396,881

## Abstract

PROJECT ABSTRACT/SUMMARY (From the Parent Grant)
Invasion is one of the most detrimental features of all cancers, including breast cancer, as it allows cells to
escape the primary site and form metastases at distant organs. Despite progress in prevention and early
lesions detection, the mortality associated with metastatic breast cancer is still extremely high. This is
especially true for patients presenting with triple negative breast cancer (TNBC, characterized by lack of
expression of ER, PR, and Her2), which is the most aggressive and deadliest subtype of breast cancer and the
one that so far lack specific targets for therapeutic intervention. Understanding the mechanisms that facilitate
the invasion of tumor cells will enable us to design more efficient therapeutic strategies to prevent or reduce
metastasis.
Our group has established a fundamental connection between GTP metabolism and tumor cell invasiveness;
we have unveiled GTP and its metabolic enzymes (GME) as key players in tumor progression and metastatic
potential. We have developed unique fluorescent reporters for intracellular GTP that have allowed us to
determine that, in live cells, the intracellular GTP distribution is not uniform, and brought forward the hypothesis
that local concentration of GTP can influence GTP-dependent processes. In particular, we have previously
shown that genetic or pharmacological modulation of the GTP metabolic pathway deeply affected the
activation status of small GTPases of the RHO-family and, with it, the tumor cells' invasive capability. Thus, in
Aim 1 we will explore a novel mechanism of G-proteins activation based on GME subcellular localization.
Our preliminary results showed that the rate-limiting enzyme for GTP de novo production, inositol
monophosphate dehydrogenase 2 (IMPDH2) enriches at cell membrane sites that are critical for cell migration
and invasion (namely focal adhesion, FA, and invadopodia). The role of IMPDH2 at these sites is virtually
uncharacterize

## Key facts

- **NIH application ID:** 11127917
- **Project number:** 4R37CA248018-06
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Anna  Bianchi-Smiraglia
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $396,881
- **Award type:** 4N
- **Project period:** 2025-12-01T00:00:00 → 2028-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11127917

## Citation

> US National Institutes of Health, RePORTER application 11127917, Leveraging the GTP Biosynthetic Pathway for Anti-Tumor Therapies (4R37CA248018-06). Retrieved via AI Analytics 2026-07-02 from https://api.ai-analytics.org/grant/nih/11127917. Licensed CC0.

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