Systematic genome-wide RNAi screen to identify novel synthetic lethal interactions in human breast cancer cell lines: implications for the development of therapeutic molecular targets.

• Applicant: Eva Maria Murga Penas, Ph.D.
• Subject Area: Hematology, Oncology
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 187319425

Cancer is a heterogeneous disease that arises from an accumulation of genetic and epigenetic alterations resulting in a failure of cells to respond correctly to diverse signals, such as control of proliferation, differentiation, adhesion and apoptosis. Most chemotherapeutic treatments are based on drugs that affect unspecifically the rapidly growing tumor cells and a variety of normal cells producing, therefore, severe side effects. Novel anticancer therapies are focused on treatments that selective kill cancer cells while sparing normal cells and therefore are less toxic. The application of the RNAi technology for discovering of tumor cell specific vulnerabilities is a novel strategy that will help to the development of more rational therapies in cancer treatments. In this project, I will conduct a gene silencing strategy to introduce specific perturbations to compromise the homeostasis of breast cancer cells without affecting normal ones. For this purpose, a second-generation of shRNA library of 70,000 short hairpin RNAs will be used as a perturbation method to search the entire genome for genes that are required to maintain the viability of different breast cancer cells (basal, luminal, and non-transformed cell lines).This project exploits the RNAi technology to identify genes that, when silenced, exclusively reduce the viability of breast cancer cells that carry preexistent genetic alterations without affecting normal cells. Thus, the successful completion of this research plan will provide novel targets for more efficient and less harmful breast cancer therapies.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Jose M. Silva, Ph.D.