Finding new targets in non-tumor cells that make IBC tumor cells easier to target.

The long-term goal of our research is to reduce the mortality of patients with IBC by developing a novel personalized, targeted therapy. This research will expand our understanding on how inflammasome responses in tumor cells affect its surrounding cells in the tumor microenvironment to modulate tumorigenicity and how this crosstalk can be used to develop new therapeutic strategies for IBC patients. Our study will justify conducting clinical trials targeting inflammasome for patients with IBC and lead to improvement of overall survival. Further, we can apply the obtained knowledge to other inflammation-driven cancer.

The project will be led by Dr. Jason Lee, who is the Team Leader and Senior Research Scientist in charge of the EDGE (Enhanced Drug-development Guidance and Evaluation) Preclinical Solutions in the Breast Medical Oncology division at MD Anderson.

The money Houston’s Hunt for Hope raises will go directly to funding this exciting research to be conducted at MD Anderson.  Importantly, the costs of the event have been underwritten, so all the funds raised will go to financing this hopefully life-saving and life-extending research project.

The proposed preclinical research for targeting inflammasome in inflammatory breast cancer is described as follows:

Inflammatory breast cancer (IBC) is a very aggressive type of advanced breast cancer. It accounts for 10% of breast cancer deaths. IBC can initially present as either stage IIIB/IIIC locally advanced or stage IV breast cancer in one-third of cases. The standard treatment for IBC is neoadjuvant combination chemotherapy followed by surgery then radiotherapy. However, the 10-year survival rates after diagnosis are only about 20-35%. Thus, an important strategy to improve outcomes for IBC patients is to develop new treatments for patients with this disease.

The MD Anderson group reported that inflammation contributes to aggressiveness of IBC by secretion of inflammatory molecules (called cytokines/chemokines) from cancer itself or cancer surrounding normal cells. Some specific inflammatory molecules detected in patient serum and reported as an indicator for the risk of carcinoma and the prognosis of established cancers.

The inflammasome is a multiprotein complex that activates inflammatory response for host defense (inflammation). Dysregulation of Inflammasome function has been shown to be a driver of chronic inflammatory diseases and has been known to play a causative role in many of the inflammasome-related diseases. Currently, we are investigating the inflammasome response as a pharmaceutical target candidate for the development of personalized, targeted therapy for IBC. The roles of the inflammasome in cancer progression and metastasis have been intensively investigated during the last few years. However, in spite of the importance of the communication between a tumor and its surrounding cells in tumorigenicity, there has been limited research on the roles of crosstalk between a tumor and its neighboring cells in inflammasome responses. Our central hypothesis is that Inflammasome-mediated crosstalk between a tumor and its surrounding cells promotes IBC progress, which is a highly exploitable therapeutic target for IBC.

The specific objectives of this study are to investigate 1) how pro-inflammatory molecules regulate inflammasomes in IBC cells to affect their tumorigenicity and 2) investigate the anti-tumor effects of inflammasome inhibitor in IBC using preclinical models. We will test our central hypothesis and accomplish the objectives of this application by pursuing the following two specific aims:

Aim 1: Determine how pro-inflammatory modulates the inflammasome response by the interaction between IBC cells and its surrounding cells

Aim 2: Develop an effective inflammasome-targeted therapeutic approach for IBC

We appreciate the time, talents, efforts and expertise our researchers will be devoting to this project.  They believe this project to be promising and will be keeping us all informed as to their progress.