Originally awarded to Maria Giuseppina Baratta, PhD
Ovarian cancer is the leading cause of death from gynecologic malignancy in the U.S. Although response rates to initial surgery and platinum-based therapy can be 70-80%, the disease recurs in most patients and becomes increasingly platinum-resistant. Subsequent treatment with traditional single-agent chemotherapy results in response rates of approximately 20% at best, with a median time-to-progression of 2 to 3 months. New treatments are thus greatly needed, and the arena of targeted therapy is of great interest.
Recent data from the The Cancer Genome Atlas have revealed that high-grade serous ovarian cancers have limited point mutations aside from TP53, and significant alterations to multiple genes due to genomic amplifications or deletions. Despite how many genetic alterations have been described, very few targeted therapy have entered clinical trials. The main purpose of a targeted therapy is to impair the function of a gene that is essential for the survival of the cancer cell. In order to find these essential genes, I designed an experimental strategy aimed to test the role of a gene on the survival of a human ovarian cancer cell while growing into a tumor in a mouse. Indeed, I reasoned that cancer cell’s ability to survive had to be tested in an environment as close as possible to the physiological one. The approach I set up allowed me to screen the function of about 200 genes simultaneously in a single mouse-bearing tumor. I screened a total of 800 genes, including all human kinases and 300 putative human oncoprotein and found ~40 potential new druggable candidate genes. I now propose to test the function of these candidate target genes in Primary Ovarian Cancer cells and in tumors deriving from these cells. In addition, I propose to identify clinical characteristic that would predict sensitivity to a certain gene in order to identify a suitable population of patients that could benefit from a certain targeted therapy.