# Project 3 - Deciphering the Role of the Translational Oncogenic Program in Prostate Cance

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $511,680

## Abstract

PROJECT SUMMARY/ABSTRACT – PROJECT 3 (RUGGERO): DECIPHERING THE ROLE OF THE
TRANSLATIONAL ONCOGENIC PROGRAM IN PROSTATE CANCER
While the approved treatments for castrate-resistant prostate cancer (CRPC), such as chemotherapy and
androgen signaling inhibition (ASI), confer significant survival benefits, up to 30% of patients have primary
refractory disease and, inevitably over time, all patients experience disease progression. There is an urgent
need for the development of novel alternative therapies that may be combined with, or used in place of,
conventional androgen receptor (AR)-targeted approaches. Recently we have discovered that phosphorylation
of eIF4E at serine 209 (P-eIF4E) by the MAP-kinase interacting serine/threonine kinase 1 and 2 (Mnk1/2) is
essential for prostate cancer (PCa) development. However, the role of eIF4E phosphorylation in PCa
development and the mechanisms by which P-eIF4E contributes to oncogenesis remain poorly understood. In
this proposal, we seek to address the outstanding question of how human metastatic PCa cells tailor their
proteome via regulation of eIF4E activity, and to unveil the therapeutic benefits of targeting eIF4E in the lethal
state of castration resistance. We propose to explore this question with the following aims: (1) Targeting the
eIF4E-dependent translational oncogenic program in a pre-clinical metastatic CRPC model; (2) To undertake a
clinical trial to examine the effects of tomivosertib in combination with enzalutamide in patients with metastatic
CRPC; (3) To characterize novel eIF4E interacting partners in PCa that may modulate eIF4E-dependent
therapies. Important to the completion of these aims, several interaction hits that confer sensitization to
tomivosertib therapies already have been identified in our laboratories. With this knowledge, we believe that we
are in a unique position to implement rational and highly specific compounds for translation control as novel
therapies for metastatic PCa.

## Key facts

- **NIH application ID:** 10769617
- **Project number:** 1P50CA275741-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Davide Ruggero
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $511,680
- **Award type:** 1
- **Project period:** 2024-09-02 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769617

## Citation

> US National Institutes of Health, RePORTER application 10769617, Project 3 - Deciphering the Role of the Translational Oncogenic Program in Prostate Cance (1P50CA275741-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10769617. Licensed CC0.

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