# Evaluation of voltage-gated calcium ion channels as a therapeutic target in intrahepatic cholangiocarcinoma

> **NIH NIH F32** · DUKE UNIVERSITY · 2022 · $76,234

## Abstract

Project Summary/Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary liver cancer with a median overall survival of
11.7 months. The majority of patients present with unresectable disease, demonstrating a significant need for
improved systemic therapies. Here, we use CRISPR/Cas9 screens to identify genes essential to ICC survival
that could serve as novel therapeutic targets. We demonstrate that CACNA1A and CACNA1G, which encode
the main pore-forming subunits of two voltage-gated calcium ion channels (VGCCs), are two genes of
essentiality in five ICC cell lines. We hypothesize that aberrant expression of voltage-gated ion channels is
essential to ICC survival and propose that existing FDA-approved calcium channel blockers could be
repurposed to treat ICC. Our preliminary data demonstrate that not only are these two genes essential to ICC
proliferation, but also that both antihypertensives and antipsychotics may be effective in decreasing ICC
viability in vitro. To test our central hypothesis, we propose the following aims: 1) determine the effect of VGCC
genetic knockdown and pharmacologic blockade on ICC cells in vitro, 2) investigate the mechanisms by which
blockade of these calcium channels decreases ICC viability, and 3) determine whether calcium channel
blockers can be used individually or to augment the effects of chemotherapy both in vivo and in novel patient-
derived models.

## Key facts

- **NIH application ID:** 10386735
- **Project number:** 1F32CA268527-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Annie Liu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $76,234
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386735

## Citation

> US National Institutes of Health, RePORTER application 10386735, Evaluation of voltage-gated calcium ion channels as a therapeutic target in intrahepatic cholangiocarcinoma (1F32CA268527-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10386735. Licensed CC0.

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