More than 14,000 patients in the United States die of ovarian cancer each year, making this cancer the fifth leading cause of cancer death among women in the United States. Within different subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSC) presents as an aggressive advanced-stage disease, limiting the opportunity for clinical intervention. Although most of the patients’ tumors shrink during treatment (chemosensitive tumor), some patients’ tumors continue to grow during treatment (refractory tumor), and some patients’ tumors come back within six months after finishing treatment and die within a short period of time (resistant tumor).
Therefore, it is of paramount importance to understand why some tumors are sensitive to anti-cancer drugs such as carboplatin and paclitaxel treatment and some are not, so that new drugs can be developed to improve the survival rates of these patients. Recent studies show that the presence of one cell type of the immune system that expresses a molecule called CD8 (CD8+ cell) in the tumor tissue can make patients with HGSC survive longer than those without. In spite of these findings, the reason why CD8+ cells can make the tumor more sensitive to drug treatment, and whether there are other cell types of the immune system that are associated with drug sensitivity, have not been thoroughly explored. Recent innovations in high-throughput analytical techniques of patient-derived specimens may address the clinical challenges described above.
However, these techniques that analyze proteins, RNA, metabolites, and immune cells have numerous limitations that currently hamper their utility in the clinical management of HGSC. Major confounders are the high heterogenicity of both the tumor as well as the resolution of these techniques. To overcome these limitations, we propose to combine the-state-of-the-art immune profiling technique with cutting-edge spatial transcriptomics technique to identify immune cell subtypes associated with chemoresistance. One of the major issues in the identification of an immune system cells is that multiple markers need to be used to define a particular immune cell type. One newly developed method that we plan to use, called Imaging Mass Cytometry (IMC), can help to solve these issues. This method can detect over 40 markers simultaneously on a tumor tissue section using metal-tagged antibodies that can recognize these proteins. Next, we would like to ask why certain immune cell-related features identified in the tumor tissue can make the tumor cells more sensitive or resistant to routine drug treatment. We propose to address this question by using another state-of-the-art technique called Spatial Transcriptomics (ST) combined with newly developed Artificial Intelligence methodologies, which will allow us to determine the gene expression pattern of a single cell in a particular location of a tumor tissue. IMC and ST will ultimately allow us to develop strategies targeting the communication mechanisms between immune cells and their neighboring cells, making the tumor cells more sensitive to routine anti-cancer drugs, with the final goal to improve survival rates in HGSC patients.
This grant was made possible in part by a generous donation from Benton Clark in loving memory of Johanna M. Clark, and by Jonathan Sockolosky.
Dr. Sammy Ferri-Borgogno is currently a postdoctoral research fellow in the laboratory of Dr. Samuel Mok in the Department of Gynecologic Oncology and Reproductive Medicine at UT MD Anderson Cancer Center (MDACC), where she is devoted to elucidating immune landscapes and crosstalk signaling networks that interplay in the ovarian tumor microenvironment to modulate clinical outcomes.
Dr. Ferri-Borgogno earned a Bachelor of Science degree in Biotechnology and subsequently a Summa Cum Laude Master of Science degree in Medical Biotechnology from the University of Turin, Italy, where she characterized the role of alpha-enolase in pancreatic ductal adenocarcinoma. Dr. Ferri-Borgogno studied how cancer biology, -omics technologies and immunology might be integrated to understand host-tumor responses and identify new diagnostic markers and therapeutic targets for solid tumors under the guidance of Prof. Francesco Novelli during her doctoral training at the University of Turin, Italy. Her thesis work demonstrated the functional relevance of ENO1 inhibition in human cancer cell lines through proteomic, biochemical and functional approaches. Dr. Ferri-Borgogno started her postdoctoral training in the laboratory of Dr. Anirban Maitra at MDACC with the goal of develop and expand her passionate interest in cancer biology as well as explore a more translational research approach. Here she focused her attention on characterizing the pivotal role of two main epigenetic regulators in pancreatic cancer, ARID1A and MLL3.
Recently, her willing to explore new fields and to expand her research knowledge in cancer biology, made Dr. Ferri-Borgogno to join the laboratory of Dr. Samuel Mok. As a senior post-doctoral fellow in the lab she has primary responsibility for all research initiatives and projects related to clarify the molecular/cellular interactions existing between stromal cells and cancer immunity to identify markers in the ovarian tumor microenvironment that can simultaneously normalize aberrant angiogenesis and increase tumor immune cell activation and infiltration, thus resulting in significant treatment outcomes. To demonstrate her hard work in the field of ovarian cancer, and recognize her research excellence, Dr. Ferri-Borgogno was awarded the 2020 Diane Denson Tobola Fellowship in Ovarian Cancer Research at MD Anderson Cancer Center.
With the support of the Ovarian Cancer Research Alliance, Dr. Ferri-Borgogno will utilize cutting-edge technologies such as Spatial Transcriptomics (ST) and Imaging mass cytometry (IMC) to identify biomarkers and molecular mechanisms associated with chemoresistance in ovarian cancer.