Seino M, et al. J Gynecol Oncol. 2023 Nov;35(1):e15. https://doi.org/10.3802/jgo.2024.35.e15

Background: Globally, cervical cancer is the fourth most common cancer in women. Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer, an extremely rare and treatment-resistant condition. Case presentation: A 64-year-old Japanese woman presented with genital bleeding. She was diagnosed as having stage IB1 squamous cell cervical cancer and subsequently treated with radiotherapy. Approximately 2 years after the curative radiotherapy, she developed itching, skin rash, and small nodules on her left femoral and pubic area. Slight ¹⁸F-fluorodeoxyglucose uptake was detected at her left femoral skin on positron emission tomography with computed tomography. A histopathological examination was performed on a biopsy sample from an erythematous macule on her left femoral skin and vulva. Consequently, she was diagnosed as having cutaneous lymphangitis carcinomatosa arising from cervical cancer. Paclitaxel (135 mg/m²), cisplatin (50 mg/m²), and bevacizumab (15 mg/kg) combination therapy was administered every 21 days. Both itching and rash improved after three treatment cycles. After the completion of six cycles, skin erythema in the femoral and vulval area disappeared completely. Our patient experienced a 25-month symptom-free interval after the last chemotherapy session. Conclusion: Our findings suggest that combination chemotherapy plus bevacizumab is an effective therapeutic option in patients with cutaneous lymphangitis carcinomatosa arising from cervical cancer.

Https://doi.org/10.18632/oncotarget.28185 Kanako Sendo, Manabu Seino, Tsuyoshi Ohta, Satoru Nagase

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant, which protects cells against reactive oxygen species (ROS). High levels of GSH are related to chemotherapeutic resistance. The glutamine/cystine transporter xCT is essential for intracellular GSH synthesis. However, whether xCT inhibition can overcome the resistance to chemotherapeutic agents in OCCC remains unclear. This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS. Moreover, combined treatment with PTX and SAS induced ferroptosis in the cells with low expression of glutathione peroxidase (GPx4), high levels of intracellular iron and significant lipid ROS accumulation. Therefore, our findings provide valuable information that the xCT inhibitor might be a promising therapeutic target for drug-resistant OCCC. The strategy of combined administration of PTX and SAS can potentially be used to treat OCCC and help to develop novel therapeutic methods.

Seino M, et al. J Gynecol Oncol. 2022 Sep;34(1):e4. https://doi.org/10.3802/jgo.2023.34.e4