# Targeting PCSK9 axis for castration-resistant prostate cancer recurrence suppression

> **NIH NIH R21** · UNIVERSITY OF LOUISIANA AT MONROE · 2022 · $182,419

## Abstract

SUMMARY
Metastatic castration-resistant prostate cancer (mCRPC) is the most recurrent and, fatal
phenotype. mCRPC patients have poor recurrence-free and limited preventive options. The
natural product pseurotin A (PS) dually suppressed PCSK9 secretion and interaction with LDLR.
PS suppressed 94% of PC-3 PC recurrence in nude mice model. PS antimigratory activity
significantly reduced when PCSK9 knocked-down. The small molecular size of PS is
advantageous over the FDA-approved humanized PCSK9 mAbs acting intra- and extra-cellular
unlike the later which can act extracellular only, reflecting better potency. Recently, PCSK9
proved critical driver for prostate and several other cancers. Project central hypothesis is
targeting extra- and intracellular PCSK9 axis with the small molecule PCSK9 inhibitor
pseurotin A can effectively prevent mCRPC recurrences and therefore PS can be
developed as effective recurrence preventer in mCRPC survivors. Aim 1: Efficacy of PS to
prevent mCRPC recurrence in nude mice and PCSK9 validation as a pathogenesis marker in
human PC tissues microarray. Assessments will compare PS potency in wild and PCSK9-
knockdown CWR-R1ca cells in adjuvant (post-primary tumor excision) mode and after
neoadjuvant enzultamide- docetaxel regimen followed by primary tumor surgical excision in nude
mice models. Biomax human tissue microarray will be used to validate PCSK9 relevance in
human PC. Aim 2: Assess the PS safety and pharmacokinetics in Swiss albino mouse models.
Expected outcomes: Proposed studies entail PS validation as a novel targeted intervention for
mCRPC recurrences prevention. PCSK9 targeting is a novel therapeutic alternative for long-term
prevention of metastatic castration-resistant prostate cancer recurrence in prostate cancer
survivors.

## Key facts

- **NIH application ID:** 10429627
- **Project number:** 1R21CA263290-01A1
- **Recipient organization:** UNIVERSITY OF LOUISIANA AT MONROE
- **Principal Investigator:** KHALID A EL SAYED
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,419
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429627

## Citation

> US National Institutes of Health, RePORTER application 10429627, Targeting PCSK9 axis for castration-resistant prostate cancer recurrence suppression (1R21CA263290-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10429627. Licensed CC0.

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