Msi2 Regulates the Aggressiveness of Non-Small Cell Lung Cancer (NSCLC)
Abstract
Scientific objective and rationale for the proposed project: Lung cancer poses a huge public health burden and is a major cause of death and suffering from cancer. Patients diagnosed with advanced non-small cell lung cancer (NSCLC) often respond poorly to initial treatments, and even less so to subsequent therapies. Unfortunately, many patients present at advanced stages, experience toxic side effects to some of the potent drugs used to try to treat these devastating disease, and eventually die from metastatic disease. There is an urgent need for better understanding of the mechanisms that drive metastasis, and not only for new treatment approaches, but also for better understanding why some tumors respond well to new drugs, while others do not. My proposal focuses on two relevant Areas of Emphasis, including better understanding of molecular mechanisms of lung cancer progression and lung cancer response to treatments. In brief, in my preliminary studies using a mouse lung cancer model, I identified the Musashi-2 protein (Msi2) as being very important for invasion and metastasis of NSCLC cells both in cultured cells and in living mice, and I began to understand the mechanism by which it worked, through control of two other proteins (TGF-beta and Notch). I also analyzed patient samples and found evidence that Msi2 is made at higher levels in human NSCLC than in normal lung tissue. I am convinced that Musashi-2 is important in a subset of patients, in making their tumors advance to become invasive, metastatic, and hence lethal. In the proposed work, I will directly analyze Msi2 function in human cell lines and emphasize understanding how levels of Msi2 affect response to drugs that target TGF-beta and Notch. These promising drugs, recently developed, are now in clinical trials; my work is intended to help match these drugs to patients most likely to benefit. Principal Investigator s career goals in lung cancer research: My career goal is to become a national leader in lung cancer research, both in lab research and clinical trial areas. I am a clinician by training, but did my PhD at MD Anderson, studying cancer biology in the lab under the direction of Dr. Jean-Pierre Issa, a well-known physician scientist. During clinical oncology training, I joined the lung cancer lab of Dr. Kurie, which led to the work proposed here. After completing my training in 2013, I joined Fox Chase Cancer Center, well known for its strong laboratory science, as a junior faculty member. My responsibilities include seeing lung cancer patients and conducting laboratory research that could be translated back to clinic and to patients. Fox Chase has provided me with very strong mentors with expertise in basic, translational, and clinical trial research, laboratory space, 70% protected time for lab research, and sufficient money to support one lab technician. The Career Development Award would be essential for supporting ongoing lab research and assure my protected time. Importantly, I am the only researcher ever to have identified a role for Msi2 in regulation of fundamental signaling pathways in lung cancer. With the resources provided by the award, I will be able to fully characterize the mechanism by which Msi2 works and begin to exploit this information clinically, testing the importance for response to newly emerging, targeted therapies, and to understand how Msi2 expression relates to the disease characteristics of real patients. This will provide me with exposure to every element of translational research and may allow me to launch a clinical trial based on my findings. Ultimate applicability of the research: The proposed research will help patients with the most common type of lung cancer, adenocarcinoma of the lung. In addition, military Service members develop lung cancer at a much higher rate than the general population, making it highly relevant to many people. I hope to develop better understanding of the new m
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510192
Entities
People
- Yanis Boumber
Organizations
- United States Army
- University of New Mexico