Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.

Immunotherapy in Ovarian Cancer: Thinking Beyond PD-1/PD-L1

Ovarian cancer (OC) is the most lethal gynecologic malignancy, affecting approximately 1 in 70 women with only 45% surviving 5 years after diagnosis. This disease typically presents at an advanced stage, and optimal debulking with platinum-based chemotherapy remains the cornerstone of management. Although most ovarian cancer patients will respond effectively to current management, 70% of them will eventually develop recurrence and novel therapeutic strategies are needed. There is a rationale for immune-oncological treatments (IO) in the managements of patients with OC. Many OC tumors demonstrate tumor infiltrating lymphocytes (TILs) and the degree of TIL infiltration is strongly and reproducibly correlated with survival. Unfortunately, results to date have been disappointing in relapsed OC. Trials have reported very modest single activity with various antibodies targeting PD-1 or PD-L1 resulting in response rate ranging from 4% to 15%. This may be due to the highly immunosuppressive TME of the disease, a low tumor mutational burden and low PD-L1 expression. There is an urgent need to improve our understanding of the immune microenvironment in OC in order to develop effective therapies. This review will discuss immune subpopulations in OC microenvironment, current immunotherapy modalities targeting these immune subsets and data from clinical trials testing IO treatments in OC and its combination with other therapeutic agents.

Behaviour and Prognosis of Ovarian Cancer With Rare Metastatic Sites

Purpose: Ovarian cancer is the commonest gynecologic malignancy in Egypt. Although metastasis from ovarian cancer is common, there are still sites with rarely reported deposits as non-regional nodes, bone, and brain. Methods: This is a chorort study were we retrospectively a group of patients over 7 years period recruited from the data system of a cancer centre. All the recruited patients suffered a rare distant metastasis from ovarian cancer. Results: Nearly half of the patients already had metastasis at the time of the initial presentation, while the rest developed during the disease course. Debulking was feasible in nearly half of the patients with long overall and progression-free survival. Tumours with non-regional nodal metastases tend to have excellent survival. Conclusion: we recommend offering these patients optimal debulking and considering those with a non-regional nodal spread as having a curable disease.