About This Project
70% of breast cancers are estrogen receptor α (ERα)-positive. ERα is the antenna that senses the ovarian hormone estrogen (E2) and drives tumour cell proliferation and spreading. 4OH-tamoxifen and faslodex are given to patients to prevent cancer growth and spreading but they possess serious side effects. Thus, additional drugs are needed to fight breast cancer. We will explore existing drugs for the possibility of ‘reuse’ as breast cancer drugs.
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What is the context of this research?
4OH-tamoxifen and faslodex differentially affect ERα content in breast cancer cells with 4OH-tamoxifen increasing ERα levels and faslodex reducing it. Thus, in principle all drugs changing ERα levels in breast cancer cells have the potential to kill them. I screened 900 FDA-approved drugs for the use in a variety of diseases and identified 9 compounds modifying ERα levels and preventing breast cancer cell proliferation. Among them, emetine, an anti-parasitic drug, and carfilzomib, a drug used against multiple myeloma, reduce ERα content, block E2-induced proliferation and kill breast cancer cells, including those resistant to 4OH-tamoxifen. Results can be read in https://link.springer.com/arti... and in http://www.sciencedirect.com/s... as published papers.
What is the significance of this project?
A novel anti-cancer agent requires, after the discovery steps, four phases of clinical trials to move from the bench to the bedside. This process is expensive, slow and time-consuming. A shortcut to the identification of new drugs for ERα-positive breast cancer treatment is searching for off-label effects in existing drugs already approved for use in humans. This drug-repositioning approach can provide safe and already-tested compounds that could be used for clinical trials for breast cancer treatment. Therefore, if this project works and we are able to identify already existing drugs as novel anti-breast cancer medicines, these compounds will ultimately increase the therapeutic options for the treatment of ERα-positive breast tumours in hospitals.
What are the goals of the project?
Once identified (e.g., drugs for heart and infectious diseases) , there is a need to test the drug efficacy in an in vivo experimental animal model. Following to the 3Rs Principles (Refinement, Reduction and Replacement), the use of mice as models to test drugs must be reduced. Alternative to mammals is the xenograft model of Zebrafish (a fish). This fish, which is commonly used to test the efficacy of anti-cancer drugs, is alternative to mice as it offers many advantages including low costs, rapid time of experimentation and responses to drugs like those obtained with mice.
I want to test one or more of the 9 identified drugs for its ability to prevent ERα-positive breast cancer cell proliferation in a xenograft model of Zebrafish.
Budget is requested for the ZeOncoTest service offered by ZeClinics (http://www.zeclinics.com). The ZeOncoTest consists in the injection of breast cancer cells in Zebrafish embryos followed by their treatment with one (or more!) of the identified molecules in order to evaluate if tumour cells still proliferate in the presence of such drugs.
As soon as I have the possibility, I will perform the planned experiments by accessing to the services offered by ZeClincs. I plan to begin as soon as the fundraising campaign ends.
Sep 23, 2017
Jan 31, 2018
Complete of the Zebrafish experiments.
Jul 31, 2018
Publication of a scientific paper where I plan to aknowledge all the backers.
Meet the Team
My team aims to help curing breast cancer by identifying compounds affecting ERα stability and preventing breast cancer cell proliferation thus providing alternativetreatments for patients.
The heart of my team is composed by:
Claudia Busonero is a Ph D student under my supervision and is primarily involved in the proposed project.
Stefano Leone is a Technician in the Department of Science and he has great enthusiasm about the possibility to found novel anti-breast cancer drugs.
I am an Associate Professor in the Laboratory of Animal and Cell Physiology, Department of Science, University of Rome ‘ROMA TRE’, Rome Italy. My work focuses on the molecular mechanisms of estrogen receptor biology in the regulation of cell physiology. Recently, I realized that the modulation of estrogen receptor levels in breast cancer cells is a novel pharmacological target. I introduced this novel idea in the scientific literature and I tried to challenge this concept by using drugs that are intended for human diseases different from breast cancer. I have obtained encouraging results that prompted me to move from in vitro research to animal models.
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