Ovarian cancer is notoriously hard to treat, ranking as the fifth leading cause of cancer deaths in women. Diagnosis often does not come until the disease has already progressed, making it significantly more difficult to treat. Because of this, many medical professionals have been researching methods to improve treatment options and patient outcomes for ovarian cancer. One example is a team of researchers from University of California (UC), San Diego, School of Medicine, Moores Cancer Center at UC San Diego Health, La Jolla Institute for Immunology, and other collaborators. They performed a study in mice models of ovarian cancer that illustrated a new strategy to treat the form referred to as high-grade serous ovarian carcinoma (HGSOC).
About the Study
Titled “Tumor FAK orchestrates immunosuppression in ovarian cancer via the CD155/TIGIT axis,” this study was published in the Proceedings of the National Academy of Sciences and focused on HGSOC – a malignancy characterized by minimal response to checkpoint inhibitor immunotherapies, microenvironment of tumors that suppress the immune system, and higher expression of checkpoint pathway ligands, which then makes it even more difficult for the immune system to attack and kill malignant cells. The team of researchers were aware that the majority (70%) of HGSOC tumors express the gene responsible for encoding focal adhesion kinase (FAK). They also know that higher FAK levels relate to poor patient outcomes.
Armed with this knowledge, the researchers then turned to their study. They utilized a mouse model of an aggressive form of ovarian cancer, a transcriptomic analysis of databases focused on ovarian cancer, and multiplex immunofluorescence assays and discovered something related to FAK: it regulates CD155 expression. CD155 is a checkpoint ligand for TGIT, which is a immunoreceptor of the T cells.
This discovery brought them to a new treatment strategy for this aggressive form of ovarian cancer. They combined a TGIT antibody capable of blocking the function of the immunoreceptor with an oral FAK inhibitor. When administered to the mouse models, they observed increased survival spurred by a significant anti tumor response.
The lead author of the study, Duygu Ozmadenci, PhD, explains the science behind this positive response. Because HGSOC creates an environment in which malignant cells are able to hide from the immune system and attack healthy cells, their goal was to mobilize the immune system to get around HGSOC’s protection. Inhibiting checkpoint receptors allows the immune system to actually practice anti tumor activity. This is why they combined the TGIT antibody with a FAK inhibitor.
Overall, the researchers observed very positive results within their study: immune system activation, positive anti tumor immune response, prolonged survival, and shrinking tumors. The next step is to study this treatment combination in clinical trials to see if it provides the same results in human patients.
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About Ovarian Cancer
As the name suggests, ovarian cancer forms in the ovaries, two organs besides the uterus that store eggs and produce hormones. There are four forms of this cancer: small cell carcinoma of the ovary (SCCO), germ cell carcinoma tumors, epithelial tumors, and stromal carcinoma tumors. While all of these types differ slightly in the symptoms they cause, common effects include abdominal swelling, loss of appetite, bloating, urinary symptoms, and pelvic pain. Medical professionals are unsure as to what exactly causes this cancer and the accompanying symptoms, but they have identified a mutated gene that raises one’s chance of developing ovarian cancer: the BRCA gene.
Surgical removal of the Fallopian tubes, ovaries, omentum, uterus, and nearby lymph nodes is the major form of treatment for this cancer. In some cases, doctors only have to remove one ovary and Fallopian tube. Other treatment options include chemotherapy, medications, and radiation therapy.