Piecing the Puzzle Together: Unraveling the Genomic Landscape of Low-Grade Serous Ovarian Carcinoma (LGSOC) to Guide Novel Therapeutic Strategies
Abstract
Ovarian cancer is the most lethal gynecological cancer, with 14,070 women dying from disease in the USA alone in 2021. Our laboratory focuses on a rare type of ovarian cancer called low-grade serous ovarian carcinoma (LGSOC) that accounts for approximately 5% of all ovarian cancer cases. Unlike the other types of ovarian cancer, LGSOCs are diagnosed at a much earlier age (43.0 versus 62.6 years, respectively), and standard ovarian chemotherapy drugs do not work. After initial chemotherapy treatment, the cancer will return in 69% of patients, with the majority of women dying from disease within 5 years of diagnosis. Due to the rarity of this cancer, the lack of LGSOC tissue samples has impeded the cancer research communities’ efforts to conduct research. Currently, three critical gaps in knowledge preventing us from significantly changing survival outcomes for these women include: 1. What changes in tumor DNA makes this specific type of ovarian cancer different from other ovarian cancer types in which chemotherapy works well? 2. How do LGSOC turn genes on and off to allow them to distract the immune surveillance system and spread from the ovary to other sites within the body? 3. Are there proteins present on the cell surface of LGSOC cancer cells that we can target with specialized drugs or new technologies such as vaccines or immunotherapy to effectively kill them? Due to our international and national collaborations with other leading scientists in the ovarian cancer field, our laboratory has access to the largest group of LGSOC tissue and patient-derived cell line samples for research purposes (more than 200 samples) in the world. Using this critical resource we will conduct scientific experiments to address all three areas stated above. In particular, we will assess whether specific changes in the DNA of LGSOC tumors alters the ability of genes to carry specific genetic messages which gives cancer cells a survival advantage. For example, the ability to grow faster or be resistant to drugs that should kill cancer cells. Using a new technology, we will also investigate what specific proteins are present on the surface of LGSOC cancer cells and not normal cells (for example bone, ovary, and heart cells) which will allow us to design new drugs that have less toxic side effects. In addition, using specialized equipment, our laboratory is currently looking at whether 6,700 drugs can effectively kill LGSOC cancer cells. Together, by understanding the basic biology and underlying vulnerabilities of LGSOC cells, we can use this information to match drugs that target specific changes in the DNA and/or surface proteins that are unique to LGSOC cells. Our powerful study has the ability to significantly influence the survival outcomes for women diagnosed with LGSOC, and our team of leading ovarian doctors will ensure that our results will be translated to the clinic where patients can benefit. The goal of our research is to provide shifts in treatment protocols for LGSOC women by providing new insights into what drives the cancerous nature of these devastating cancers. As such, our research aligns with the mission of the OCRP to support patient centered research to treat and cure ovarian cancer in all women impacted by this disease including active Service Members/Veterans. Interestingly ovarian cancer is the most predominant gynecological cancer diagnosed in U.S. active-duty women (46.4% of cases). Hence, our research efforts have large implications for all women diagnosed with ovarian cancer, including active-duty and Veteran Service Women. Also, our study has been designed to align with several OCRP Area’s of Emphasis, including (i) understanding the basic biology of ovarian cancer, (ii) developing novel therapeutic strategies for the treatment of ovarian cancer, and (iii) improving precision medicine. For the very first time, we have the ability to transform LGSOCs from frequently incurable i
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310994
Entities
People
- Kathleen Pishas
Organizations
- United States Army
- University of Melbourne