| Principal Investigator |
Sophie Lelievre |
| International Collaborator(s) |
|
| Project Type |
|
| Project Title |
Harnessing miRNAs to prevent early breast cancer onset in Lebanese women |
| Priority Area |
Prevention |
| The Intervention |
This project aims to make use of a unique risk progression series in 3D cell culture and gradient-on-a-chip to control microenvironmental exposure to oxidative stress with which we can test and pinpoint miRNAs potentially contributing to breast cancer onset from a list obtained from Lebanese women. The approach used to identify the molecules of interest can be implemented. We hope that in future work some of the markers identified can also be implemented for use. |
| Key Facilitators |
This intervention is being piloted in Beirut, Lebanon. The Indiana CTSI is developing a program focused on reciprocal innovation that seeks to support the identification, adaptation, implementation, and evaluation of promising interventions developed at LMIC partner sites for use in Indiana. This infrastructure provides funding and other resources to adapt interventions to a US context. Additional partners include international partnership between the American University of Beirut, the Academic Model Providing Access to Healthcare (AMPATH) – including partners from Indiana University and Purdue University who are also members of International Breast Cancer & Nutrition (IBCN) that has set a global collaborative infrastructure and logistics for primary prevention research since 2010. |
| Target Population |
The target population includes young, premenopausal women below the age of 40 in Lebanon. These women are being compared for the biomarkers of risk identified to US women of similar age. |
| Process to Implementation |
This intervention has not yet been implemented in Indiana but is being piloted in Beirut. If the pilot findings show positive outcomes, potential exists to apply this intervention to low resourced clinical settings in Indiana and the US, especially to women who are in populations with heightened risk of breast cancer (as shown by specific incidence). Following identification of potential pilot sites in Indiana, this intervention could be adapted and piloted for use in the US clinical context using support from the Indiana CTSI and other health partners in Indiana, e.g. university labs, State Department of Health, IU Health, Ashkenazi, and other public health centers. |
| Key Stakeholders |
Stakeholders include patients, researchers, international partners. We anticipate that transferring to the US would require similar stakeholders who would need to be engaged within the health systems and research laboratories. |
| Scaled or Transferred? |
Now that we have gotten results through rigorous data analyses, the aim is to work toward scaling this process into the US setting within specific populations with high incidence of breast cancer. |
| Type of Research |
In the proposed project, innovation is found at different levels. Firstly, the project is grounded on preliminary data obtained from breast biopsies of a population of women that is notoriously at highest risk for breast cancer in the world, since their incidence is ~200/100,000, with no known driving genetic mutation. These results provide a unique source of molecules that might be involved in early onset of breast cancer. Epidemiology studies have indicated stress and diet to be possibly involved; they constitute two sources of oxidative stress linked to prominent reactive oxygen species (ROS). Therefore, another level of innovation is to study the impact of miRNAs on cancer onset by incorporating a state-of-the-art gradient-on-a-chip with which we can assess ROS concentration leading to a switch in miRNAs transcription, and further study in the future the synergism between ROS and other risk factors such as higher breast density that exists in premenopausal women. The third level of innovation is to use the only known tissue alteration that is necessary for cancer onset as a marker of risk induction, i.e., apical polarity loss. Our approach is combining real tissue samples and blood samples with tissue-chips (a subtype of 3D cell culture) that recapitulate breast cancer risk progression. By using 3D cell culture, we can identify miRNAs and other types of RNAs that are likely to be responsible for heightened risk for breast cancer. If found in the blood, these molecules can be used as markers of heightened breast cancer risk and possibly as markers of reduced risk following preventive interventions. This approach should be extended to other countries that have specific subpopulations with known high incidence of breast cancer so that we can identify (or confirm) specific RNA-based markers of risk by comparing results between different populations in different countries. The idea is that diversity helps pinpoint what marker(s) is specific of a given subpopulation. The more specific the populations studied, the higher the chance of identifying meaningful markers of heightened risk for breast cancer and thus, the higher the likeliness to perform tailored preventive intervention. We envision to also study the markers of risk in relation to environmental risks thus, integrating population risk in a particular environment. Other LMI countries ready to be involved are Ghana and Uruguay, and with the help of IU, Kenya. |
| Published Materials |
One published manuscript (Sci Rep. 2021 Jan 29;11(1):2626.) and two other manuscripts in preparation |
| Year Funded |
2018 |
