Endogenous Alarmins in the Progression of Melanoma
Abstract
I am very interested in understanding the microenvironment in melanoma and how tumor cells interact and control immune cells to facilitate tumor growth and progression. I believe that understanding the detailed network of signals that govern tumor biology might help to discover new potential targets for cancer treatment. I am confident that the Horizon Award will benefit me in my goal of improving current knowledge on melanoma biology and how we can tailor treatments to combat such a devastating disease. Melanoma is the most serious type of skin cancer and is one of the highest causes of cancer-related deaths in the United States. Factors like sunlight and ultraviolet rays have been associated with skin cancer development later on in life. Also, it is known that melanoma rates can be higher in active duty military personnel when compared to the general population (especially among those 45 years or older). But even though many advances in cancer treatment have been made, there are many patients that still do not respond or relapse after treatment, so it is very important that new and groundbreaking treatment strategies be developed. I believe that my research will contribute to the development of these treatment strategies, as it will help gain insight in this complex type of cancer. With Dr. Bhardwaj s mentorship and guidance, together with the collaborative and resourceful setting of the institution, I will succeed in my research and more importantly, get a step closer to becoming an independent investigator in the field of tumor immunology, especially in melanoma research. My research focuses on matrix metalloproteinase 2 (MMP-2), an enzyme whose activity has been associated with tumor progression and poorer patient outcome in several types of cancer (melanoma, colorectal, prostrate, and breast among others) and Toll-like receptors (TLRs), proteins that can induce signaling pathways that activate immune cells to induce inflammation (also associated with cancer). I have collected data that these proteins can interact and promote tumor progression by putting a break on anti-tumor immune response, suggesting that MMP-2 inhibition might reduce tumor progression. Thus, if we can understand the mechanisms by which these processes occur, we will have additional targets to be used in immunotherapy. MMP-2 inhibition (either directly or indirectly, via its interacting proteins) might be a viable additional treatment for melanoma in patients that do not respond well to current treatments or that relapse after treatment and will benefit not only melanoma patients, but might also be used for other types of cancer in which MMP-2 has a negative effect. After the research goals are met, I believe that a follow-up study will be necessary to investigate the long-term effects of the inhibition. Collectively my research and the subsequent study might take 2-3 years before any clinical applications can be developed. Active duty military personnel have higher incidence of melanoma and also are exposed to sunlight and ultraviolet light in the workplace, which could lead to the development of melanoma years after on-duty sun exposure. Thus, it is of great importance that melanoma treatment strategies be developed and my research can aid in the better understanding of melanoma biology and also might help to identify better molecules to be targeted in combinatorial immunotherapy for melanoma.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610277
Entities
People
- Luciana Rebiero Muniz-Bongers
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army