Our goal is to develop a potent therapy for pancreas cancer – an incurable disease that is resistant to traditional cancer treatments. Challenges involved in treating this disease include: i) a barrier that surrounds the cancer cells (“tumor stroma”) and limits drug access, ii) diversity among cancer cells, making it hard to find a single means of killing all cells, and iii) the harsh cancer milieu, which prevents immune cells from working. Thus, new therapies to beat these barriers are vital and T cell therapy may meet this need. We plan to collect immune cells, called T cells, from patients and in the laboratory we will train them to find and kill tumor cells that display “tumor associated antigens – TAAs” on their surface. We plan to use cells that have been trained to look for tumor cells expressing 5 different TAAs in a clinical trial where we will gauge if this therapy is both safe and active in patients. Next, to ensure that our cells retain their ability to kill in the tumor milieu we will equip them with a special switch that allows them to convert bad signals into ones that are good for our T cells. Hence, we will turn an “off” switch into an “on”. By using this tactic, we hope to boost the activity of our therapy.
The most common mutation found in patients with pancreatic cancer is a mutation in the Kras gene. However, this mutation is not sufficient for initiation and progression of pancreatic cancer. It is well known that inflammation is a risk factor for pancreatic cancer and can accelerate pancreatic cancer development. We have shown that during pancreatic inflammation, caused by cigarette smoking, stones, or other stressors, immune cells secreting a factor named IL-17 are recruited to the pancreas and are capable of inducing pancreatic cancer initiation and development. We are now interested in understanding the role of these cells in regulating pancreatic cancer stem cells induction and invasiveness. This information will be useful for pancreatic cancer prevention and treatment given the existence of commercially available monoclonal antibodies that target specifically these cells.
More than 40,000 American women die of breast cancer each year. One out of every eight women in the U.S. will develop invasive breast cancer during their lifetime. In 70% of these women, estrogen and estrogen receptor α (ERα) are key players in breast cancer diseases. Keeping this endocrine signaling function low by endocrine therapy is the best treatment right now. Yet, after 5 years, hormonal treatment stops working in more than 30% of these patients and the disease returns. Because hormone resistance is still a challenge, there are few effective therapies for these patients. We plan to study estrogen and ERα related to hormone resistance.
ERα binds DNA elements that regulate gene expression. These elements are very important in cancer development and progression. When these elements lose control, breast cancer becomes resistant to hormones. Thus, if we can find ways to understand and correct these elements in hormone resistant cells, we can find cures for ERα-positive breast cancers. The goal of this project is to understand how ERα controls DNA elements. We will identify markers to measure the presence and progression of breast cancer. Our research results may lead to new therapies that target this disease. Discoveries from this project may help with treating other cancers and may be useful for other research fields.
