Investigating Models and Mechanisms of Invasive Lobular Carcinoma
Abstract
Scientific Objective and Rationale: Invasive lobular carcinoma (ILC) is the second most common subtype of invasive breast cancer following invasive ductal carcinoma (IDC). ILC accounts for 10%-15% of all annual breast cancer, corresponding to a total number of approximately 23,000-34,000. This is more than the annual number of melanoma or ovarian cancer cases and makes ILC the sixth most common cancer type among women in the United States. While IDCs grow as round masses (lumps), ILC tumors grow as disconnected, single cells, making detection difficult by mammography. Despite having favorable characteristics (hormone receptor expression, low proliferation), patients with ILC benefit less from endocrine therapy than patients with IDC. This paradox is poorly understood, and ILC currently remains a gravely understudied disease. Although increasing evidence indicates that ILC and IDC are two different tumor types, they are treated the same in the clinic, which is unacceptable in the age of personalized medicine. Thus, better understanding of ILC biology can help devise novel, personalized therapeutic strategies. To investigate potential factors driving ILC growth and spread, we performed gene expression profiling in 131 ILC tumors with long-term clinical follow-up data. By comparing the gene expression values between tumors from patients that recurred and those that did not, we identified potential mediators of ILC disease progression. In this proposal, we are focusing on two candidates, cortactin (CTTN) and quiescin sulfhydryl oxidase 1 (QSOX1), which have been implicated in cell migration and invasion, processes that allow tumors to move around and dig into the tissue in which they reside, ultimately resulting in spread to secondary sites. Using ILC cells grown in dishes in the laboratory, we will inhibit these genes and test their effects in novel ILC-tailored assays and models that we will develop. We will also inhibit these genes in human ILC cells grown in mice and assess their potential as therapeutic targets in decreasing growth and spread of ILC tumors. Career Goals: My goal during my postdoctoral training is to expand my knowledge and expertise in translational breast cancer research and develop competence in multiple areas of biology. My ultimate goal following my postdoctoral training is to establish my own translational breast cancer research laboratory at an academic institution leading my own research team. The experiments proposed in this study will be done under the close guidance of my mentors, who are experts in translational breast cancer research. Furthermore, our collaborations with clinicians, statisticians, and physical scientists will provide me with a unique, well-rounded training opportunity. The exciting findings that will emerge from this proposal will lead me to other interesting research ideas addressing challenges in breast cancer biology and treatment. Taking advantage of the vast educational and career development resources available through the University of Pittsburgh, I will develop further professional skills necessary to become an independent breast cancer researcher and a leader in my field. Applicability and Impact: Better understanding of disease progression in ILC can lead to the design of more effective therapies and improvement of outcome for patients. Furthermore, elucidation of what makes only a subset of ILC tumors recur and spread can help decrease overtreatment of patients with tumors that will not. Our investigation of ILC drivers in novel ILC-tailored models will lead to a breakthrough in our understanding of ILC and potentially identify new treatment strategies for patients suffering from this highly understudied disease. The ILC-tailored models and assays we develop will address a critical need for the ILC research community. The availability of agents that target our candidate ILC drivers CTTN and QSOX1 will facilitate the transition of our labo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1710003
Entities
People
- Nilgun Tasdemir
Organizations
- United States Army
- University of Pittsburgh