# Anticancer Effects of a Repurposed Drug in Colon Cancer

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $381,834

## Abstract

PROJECT SUMMARY/ABSTRACT
 About 25–30% of confirmed colon cancers (CC) without detectable local or distal invasion will
eventually develop metastases, and there is currently no cure for metastatic disease. The response rates
of current chemotherapy are low, around 20%. Therefore, this study related to repurposing a drug
Pimavanserin (PIMA) for CC therapy is crucial. The strategy of using existing drugs originally developed
for another disease, promises to have high impacts on cancer patients. While reducing costs in the long
and difficult process of drug development, repurposing presents a number of other pivotal advantages
regarding known PK/PD, posology, toxicity, and safety. Elevated serotonin (5-HT, 5-hydroxytryptamine), and
its receptor levels in CC, and their signaling may be involved in promoting oncogenic activities. However, little
is known regarding the mechanism of action. 5-HT2A receptor's (5-HT2AR) selective inverse agonist PIMA is
widely used in the clinical setting for treatment of Parkinson's disease psychosis. As serotonin and its
receptor 5-HT2AR have been suggested to be involved in cell growth promotion, and the receptor expression is
high in gastrointestinal tract, we inquired about the role of PIMA in anticancer activities. We have observed
that PIMA inhibits CC cell growth and induces apoptosis by activating TGF-ß tumor suppressor functions and
antagonizing the effects of serotonin/5-HT2AR on the regulation of BCL-2 family proteins and MEK/ERK
signaling. Interestingly, our initial RNA-seq results from CC cells treated with PIMA reveal the regulation of
genes related to cell growth and apoptosis, and to TGF-ß/Smad and MEK/ERK signaling. Our initial
experiments indicate that PIMA inhibits tumor growth in an in vivo allograft model (syngeneic) with no toxic
effects. Therefore, these studies provide a strong proof-of-principle that PIMA is an effective therapeutic agent
with low toxicity for CC. We hypothesize that Pimavanserin proffers its potent anti-cancer activities in colon
cancer by inhibiting cell proliferation and inducing apoptosis through abrogating the activity of 5-HT2AR and its
crosstalk with TGF-ß and MEK/ERK signaling. Here we propose to (1) determine the functional mechanisms
of action of PIMA in suppressing tumor growth, and (2) determine the anti-cancer efficacy and mechanism of
action of PIMA in CC using a humanized mouse model with organoids and a spontaneous genetic model.
Impact: Although several chemotherapeutic agents have been introduced for the treatment of CC, they are still
fraught with side effects, limited scope, and long-term treatment failure. Repurposing non-cancer drugs with
potent anti-cancer activities is crucial to facilitate patient access to new treatment options. PIMA is
successfully used for Parkinson's disease, but it has never been explored in the treatment of solid tumors.
Therefore, this first attempt of investigating the novel anticancer functions of PIMA in CC will have a broad
imp...

## Key facts

- **NIH application ID:** 10728673
- **Project number:** 1R21CA277249-01A1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** PRAN K DATTA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $381,834
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728673

## Citation

> US National Institutes of Health, RePORTER application 10728673, Anticancer Effects of a Repurposed Drug in Colon Cancer (1R21CA277249-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10728673. Licensed CC0.

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