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Targeted Cancer Therapies

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Related Experiment Video

Updated: Jun 19, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Drug Repurposing Screen Identifies Pimozide as a ROS-Inducing Therapy With Anti-Tumor Efficacy in HNSCC PDX Models.

Shogo Okazaki¹, Shintaro Nakamura², Tomoya Soma³

¹Department of Microbiology and Immunology, Nihon University School of Dentistry, Tokyo, Japan.

|November 20, 2025

Summary

This summary is machine-generated.

Pimozide, an FDA-approved drug, effectively induces reactive oxygen species (ROS) in head and neck squamous cell carcinoma (HNSCC) cells. This drug shows promise for repurposing as a novel cancer therapy, particularly for HNSCC.

Keywords:

drug repurposing head and neck squamous cell carcinoma patient‐derived xenograft model pimozide reactive oxygen species

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Area of Science:

Oncology
Pharmacology
Biochemistry

Background:

Redox regulation is crucial for tumor survival and represents a therapeutic target.
Head and neck squamous cell carcinoma (HNSCC) cells exhibit varying resistance to oxidative stress.

Purpose of the Study:

To screen FDA-approved compounds for their ability to induce reactive oxygen species (ROS) in HNSCC.
To evaluate the therapeutic potential of ROS-inducing agents, specifically pimozide, in HNSCC models.

Main Methods:

Screening of 1161 FDA-approved compounds.
In vitro assessment of ROS induction and cytotoxicity in HNSCC cells.
In vivo studies using patient-derived xenograft models.
Mechanistic studies involving dopamine D2 receptors, STAT3/5, and early growth response 1 (EGR1).

Main Results:

Pimozide was identified as a potent ROS inducer, selectively suppressing HNSCC growth.
Pimozide demonstrated anti-tumor effects as monotherapy and in combination with paclitaxel.
Early growth response 1 (EGR1) was identified as a pharmacodynamic marker for pimozide sensitivity.
Pimozide reduced tumor burden in HNSCC xenografts, with combination therapy showing enhanced effects on tumor cell differentiation.

Conclusions:

Pimozide is a promising candidate for repurposing as a novel therapeutic agent against HNSCC.
ROS induction by pimozide offers a targeted approach for HNSCC treatment.
EGR1 serves as a predictive biomarker for pimozide response in HNSCC.