Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer with nearly 70% of patients diagnosed at stage 3 or 4, which means the cancer has spread outside of the original tumor and is metastatic. New therapies are critically needed for this type of cancer. This study (Wallace-Povirk et al., 2022) demonstrates a potent new anti-tumor therapy in mice involving lead analogs that target ovarian cancer directly, as well as indirectly by targeting the tumor microenvironment. Results demonstrated that the lead analogs studied (AGF94) significantly reduced tumor burden in the mice, accompanied by significantly decreasing M2-like macrophages. Based upon these results, lead analogs such as AGF94 may represent a potential new therapy for the treatment of advanced EOC. These studies are ground-breaking in that they provide an exciting new framework for targeting not only the tumor directly but also the immunosuppressive tumor microenvironment as an essential component of therapy. Drs. Heather Gibson and Larry Matherly of Wayne State were the lead investigators on this study and a link to the publication is below.

Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment - PMC (nih.gov)