# The role of DCLK1 in the initiation of pancreatic ductal adenocarcinoma and colorectal cancer

> **NIH NIH R50** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $89,655

## Abstract

We recently demonstrated that doublecortin-like kinase 1 (DCLK1) is a putative colorectal and
pancreatic cancer stem cell marker. We also demonstrated that DCLK1 regulates multiple
oncogenic and tumor supporting pathways and processes. Furthermore, siRNA mediated
knockdown of DCLK1 results in growth arrest of pancreatic and colorectal cancer tumor
xenografts. The DCLK1+ cell is now strongly implicated as a cell-of-origin for KRAS-driven
pancreatic cancer, and recent proteomic studies demonstrate that knock-in of KRASG12/G13
mutations into CRC cells results in specific DCLK1 upregulation. Moreover, DCLK1 is highly
expressed in CRC metastases and predicts significantly decreased survival in patients.
The proposed studies for this application are related to two NCI-funded projects.
1. The role of DCLK1 in the initiation of pancreatic ductal adenocarcinoma. We will test our
hypotheses with the experiments proposed in the following three specific aims:
Aim 1: To determine the functional and molecular mechanisms through which Dclk1+ cells initiate
pancreatic tumorigenesis.
Aim 2: To delineate the multi-compartmental role of Dclk1 deletion in pancreatic tumorigenesis.
Aim 3: To demonstrate the feasibility of targeting Dclk1 in PDAC as a therapeutic approach.
2. The role of DCLK1 in the initiation of colorectal cancer. We propose to unravel DCLK1's
role in KRAS-mutant CRC progression and assess DCLK1-targeted therapies with the following
Specific Aims:
Aim 1: Determine the role of DCLK1 and the DCLK1+ tuft cell in the initiation and progression of
KRAS-mutant colorectal cancer.
Aim 2: Dissect DCLK1's mechanistic role in CRC downstream of KRASG12D and in the
background of APC loss.
Aim 3: Demonstrate the feasibility of targeting DCLK1 in KRAS-mutant patient-derived CRC
models as a primary therapy and to overcome resistance to EGFR-targeted cetuximab and
gefitinib.
The current proposals include innovative genetically engineered mouse models of PDAC and
CRC, innovative cell lines, and innovative concepts that may lead to translational studies on
PDAC and CRC.

## Key facts

- **NIH application ID:** 10241318
- **Project number:** 5R50CA233186-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Dongfeng Qu
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $89,655
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241318

## Citation

> US National Institutes of Health, RePORTER application 10241318, The role of DCLK1 in the initiation of pancreatic ductal adenocarcinoma and colorectal cancer (5R50CA233186-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241318. Licensed CC0.

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