Project title: Role of Nrf2 in SBNET drug resistance and development of a novel inhibitor
Po Hien Ear, PhD University of Iowa
- Status: Active
- Year(s): 2024
- Grant Type: Investigator
- Research Type: Basic
- Primary Tumor Site: Multiple
- Area of Inquiry: Tumor biology and drug sensitivity
Description
What critical problem/question will researchers try to answer?
Few medical therapies are available for patients with small bowel neuroendocrine tumors (SBNETs) and the existing options are not very effective at eliminating the cancer because SBNET has a unique tumor biology. Our project will address the cause of drug resistance in SBNET and the development of a novel inhibitor to resensitize SBNET to FDA-approved anti-cancer therapies.
Why is this important?
Development of new therapies has been limited by the availability of SBNET models for drug testing. Our group pioneered a novel strategy to grow SBNET cells from patient tumors and use them for drug testing. We identified a new signaling program that makes SBNET cells drug resistant under the control of a transcription factor called Nrf2. Nrf2 serves as a “Master Regulator” to make anti-cancer drugs less potent. When we block the activities of Nrf2, we can make SBNET cells sensitive to many anti-cancer drugs.
What will the researchers do?
We will examine Nrf2 levels in many SBNET samples and genetically interfere with the Nrf2 pathway to improve response to drug treatments. In addition, we aim to develop a new drug (Nrf2 inhibitor) that will specifically get into SBNET cells, make them sensitive to the standard of care therapies, and kill off the cancer cells.
How might this improve treatment of neuroendocrine cancer?
It is well known to clinicians that SBNETs are particularly resistant to medical therapies. By blocking the actions of Nrf2, SBNET cells can no longer inactivate or flush out the drugs. Hence, the tumor cells will become weaker and will be easily killed by anti-cancer drugs. Our findings will potentially improve the treatments and survival of SBNET patients and other NETs that express high levels of Nrf2.
What is the next step?
My colleagues and I will examine Nrf2 activities in hundreds of patient tumors. We will map out the mechanism of action of Nrf2 in SBNET cells. Moreover, we will develop a cancer cell specific Nrf2 inhibitor that will have less side effects and test it in our cutting-edge in vitro and in vivo SBNET models.
Additional Details
- City: Iowa City
- State: Iowa
- Country: United States
- Grant Duration: 2 Years
- Sponsor: Carol DeBacker Charitable Trust
DISCLAIMER
NETRF funds laboratory research to understand the development of neuroendocrine tumors and translational research to explore new concepts in treatment. Research grant descriptions and research updates from NETRF are not intended to serve as medical advice. It can take years for research discoveries to be fully validated and approved for patient care. Always consult your health care providers about your treatment options.