# MELT: Modulation of PSMA Expression for Lutetium Therapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $651,214

## Abstract

Project Abstract
Castrate resistant prostate cancer is a uniformly lethal disease and, although there have been a number of
new therapeutic agents approved, there is still a large need for more effective treatments in this patient
population. In this proposal, we will study a radioligand therapy (RLT) that targets the prostate specific
membrane antigen (PSMA), a molecule that is expressed on the majority of prostate cancer cells. In multiple
small studies, PSMA RLT has shown to have remarkable efficacy in heavily pretreated patients, with over 40%
of patients having decreased PSA of over 50%. PSMA RLT relies on two basic premises: targeting the
radiation to PSMA and the radiosensitivity of the tissue to the deposited radiation. First, we will understand
how PSMA expression is regulated, allowing us to pharmacologically target cancer cells to increase their
PSMA expression. Second, we will understand whether tumors respond because of intrinsic sensitivity to
radiation or high doses of deposited radiation. This knowledge will be critical to determine if patients need
higher expression of PSMA or increased tumor cell sensitivity in order to improve the response to this therapy.
We will test treatments capable of increasing the sensitivity of tumors to radiation as well as potential therapies
that can increase expression of PSMA. This work will be used to inform the development of a clinical trial that
will involve PSMA RLT and a co-administered therapy to increase its already promising efficacy.

## Key facts

- **NIH application ID:** 10220901
- **Project number:** 5R01CA235741-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Felix Yi-Chung Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $651,214
- **Award type:** 5
- **Project period:** 2019-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220901

## Citation

> US National Institutes of Health, RePORTER application 10220901, MELT: Modulation of PSMA Expression for Lutetium Therapy (5R01CA235741-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220901. Licensed CC0.

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