Discovering novel breast cancer therapeutic targets using a CRISPR/Cas9 in vivo screening platform.


Breast cancer is the leading cause of cancer death in women worldwide (Global Health Estimates, WHO 2013). The main factors preventing improvements in mortality rates are: a) the lack of specific treatments for basal-like triple negative tumors due to the absence of therapeutic targets, b) tumor resistance to current endocrine therapies such as tamoxifen and c) lack of strategies to prevent the development of metastasis in secondary organs. The general objective of this application is to identify, through the use of an in vivo screening platform based on CRISPR/Cas9, coding genes involved in the development of primary tumors and metastases in difficult to treat breast cancer subtypes. Based on previous findings, our hypothesis is that genes involved in the evasion of the immune system may be key to the progression of breast cancer. Through the systematic measurement of the phenotypes generated by loss-of-function mutations induced by a CRISPR/Cas9 library, our main goal is: to determine which genes play relevant roles in modulating immune system responses, allowing tumor growth and metastasis in a basal model of breast cancer.

We will also explore candidate genes participating in resistance to current targeted therapy during tumor progression.

Our knowledge in the use of diverse in vivo models of breast cancer, our capacity to setup CRISPR/Cas9 mediated genome editing experiments and our knowledge to generate and analyse high throughput screenings, place us in a unique position to carry out this project. Through the proposed studies, we expect to find candidate genes involved in the progression of tumors of different subtypes, especially those currently orphan of therapeutic targets. In turn, by systematically analysing the genes necessary for the formation of metastases in lung and bone, this project will allow us to provide new potential therapeutic targets. Through the systematic study of the genes involved in various aspects of tumor biology, we intend to provide a rational basis for new specific treatments contributing to reduce deaths from breast cancer in the future.


Lugar de trabajo: Laboratorios de A.Gattelli y J.P.Fededa, en el IFIBYNE-FCEyN, UBA e IIB-UNSAM, Campus Miguelete.


Que vas a hacer y aprender? Edición génica masiva mediante el uso de la técnica CRISPR/Cas9, cultivo y ensayos con líneas celulares, trabajo con ratones, modelos de cáncer de mama in vivo e inmunología, immunohistoquímica, microscopia y técnicas moleculares.




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