Lubomir Bodnar

Hypoxia-Mediated Decrease of Ovarian Cancer Cells Reaction to Treatment: Significance for Chemo- and Immunotherapies

Hypoxia, a common factor ruling the microenvironment composition, leads to tumor progression. In this hypoxic context, cytokines and cells cooperate to favor cancer development and metastasis. Tumor hypoxia is heterogeneously distributed. Oxygen gradients depend on the vicinity, functionality of blood vessels, and oxygen ability to diffuse into surrounding tissues. Thus, the vasculature state modulates the microenvironment of the tumor cells. Cells sense and react to small variations in oxygen tension, which explains the lack of tumor cells’ unicity in their reaction to drugs. Ovarian cancers are highly hypoxia-dependent, ascites worsening the access to oxygen, in their reactions to both chemotherapy and new immunotherapy. Consequently, hypoxia affects the results of immunotherapy, and is thus, crucial for the design of treatments. Controlling key immunosuppressive factors and receptors, as well as immune checkpoint molecule expression on tumor, immune and stromal cells, hypoxia induces immunosuppression. Consequently, new approaches to alleviate hypoxia in the tumor microenvironment bring promises for ovarian cancer immunotherapeutic strategies. This review focuses on the effects of hypoxia in the microenvironment and its consequences on tumor treatments. This opens the way to innovative combined treatments to the advantage of immunotherapy outcome in ovarian cancers.

Updated Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma: The Polish Society of Gynecological Oncology (2025v)

In 2023, the Polish Society of Gynecologic Oncology (PSGO) published clinical recommendations for the diagnosis, treatment, and care of women with endometrial cancer (EC), developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. A 2025 update was initiated in response to new evidence, particularly regarding systemic therapies for metastatic, advanced, or recurrent EC, and the introduction of an updated FIGO classification. A targeted literature review identified relevant phase III clinical trials and systematic reviews, including RUBY, GY-018, AtTend, and DUO-E. These trials were critically assessed by an Expert Panel in accordance with the AGREE II methodology. Updated recommendations were formulated based on this evidence, with a comparative analysis of the old and new FIGO staging systems and visual updates to treatment pathways. Key changes include the addition of immunotherapy (I/O) plus chemotherapy (CHTH) as first-line treatment for all molecular subtypes of high-grade endometrioid and non-endometrioid carcinomas, replacing chemotherapy alone. For MMRp-positive cases, the 2025 version introduces the use of Olaparib alongside Durvalumab and CHTH. HER2-positive MMRp serous carcinoma remains eligible for trastuzumab in combination with CHTH. Second-line treatment guidance remains unchanged for patients who did not receive I/O plus CHTH initially. However, options for those previously treated with this combination are still under evaluation. This update ensures alignment with the latest international standards and reinforces evidence-based, personalized care for EC patients.