Les réseaux de signalisation des récepteurs tyrosine kinase gouvernant la progression du cancer du sein

 

Josie Ursini-Siegel

Institut Lady Davis de recherches médicales de l'Hôpital général juif

 

Domaine :   cancer

Programme chercheurs-boursiers - Senior

Concours 2017-2018

Breast cancer cells employ numerous mechanisms to develop into aggressive tumors that often become refractory to standard and emerging therapies. For example, aggressive breast tumors become unresponsive to processes that normally restrain cell growth. In order to support rapid proliferation, cancer cells must substantially increase their ability to acquire nutrients and oxygen by generating a new blood supply (neo-vascularization) and also to generate the energy (ATP) for cancer cells to divide.  Secondly, aggressive breast tumors must also evade the ability of our immune system to recognize and destroy them. They do so by inactivating the tumor killing properties of a class of immune cells, called cytotoxic T lymphocytes, which are essential to eradicate tumor cells or allow them to persist as dormant, pre-clinical lesions. In this stage, the individual remains asymptomatic. Breast tumor cells are able to become invisible to CTLs that are trying to kill them. unresponsive to checkpoints that normally restrain cell growth, develop resistance to standard and novel therapies and evade the ability of our immune system to recognize and destroy them. 

Finally, individual breast cancers are heterogeneous, which contributes to the ability of tumors to relapse and eventually lead to the development of secondary life-threatening metastases, many years after diagnosis of the first tumor.  Our research focuses on a particular class of proteins, called receptor tyrosine kinases (RTKs), which substantially increase the ability of cancer cells to recruit a new vasculature, generate ATP, evade the immune system and increase tumor heterogeneity. This research program addresses the molecular mechanisms by which RTKs regulates all stages of breast tumorigenesis with the goal to identify strategies to sensitize tumor to anti-angiogenic therapies, immunotherapies, standard of care chemotherapies or emerging targeted therapies. We also wish to identify markers that predict breast cancer heterogeneity and the likelihood to develop therapeutic resistance.