Can we defeat breast cancer by using the properties of already available medications?

$2,752
Pledged
37%
Funded
$7,500
Goal
16
Days Left
  • $2,752
    pledged
  • 37%
    funded
  • 16
    days left

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

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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.

Endorsed by

Filippo had been working in my team for more than 10 years. Together we discovered the way the estrogen receptor signals through a non-classical pathway to breast cancer cells proliferation. Now I am really excited for the new Filippo's project that is something innovative in the field of estrogen receptor-dependent breast cancer research and has tremendous clinical implications. I believe that Filippo's experiments will shed the foundation for introducing them to patients.
I have been knowing Filippo Acconcia since the beginning of his career and I am now astonished by the potential of his present discoveries. The idea to find a cure for breast cancer by taking advantages of the unknown effects of already available medicines is exiting. Filippo Acconcia has spent his interest in search of alternatives for breast cancer treatment. This study is extremely important with the percentage of breast cancer diagnosis growing rapidly within young women. I am excited to watch it funded.

Flag iconProject Timeline

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

Project Launched

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

Filippo Acconcia
Filippo Acconcia
Associate Professor of Physiology, Ph D

Affiliates

Univeristy Roma TRE
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Team Bio

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.

Filippo Acconcia

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.

Additional Information



Project Backers

  • 30Backers
  • 37%Funded
  • $2,752Total Donations
  • $91.73Average Donation
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