Platinum-based chemotherapy causes genetic damage and induces apoptosis in ovarian cancer cells. Enhancing the ability to resist platinum drug-induced DNA damage and apoptotic stress is critical for tumor cells to acquire drug resistance. Here, we found that Y-box binding protein 1 (YBX1) was highly expressed in cisplatin-resistant patient-derived organoids (PDOs) and was a crucial gene for alleviating platinum-induced stress and maintaining drug resistance characteristics in ovarian cancer cells. Mechanistically, YBX1 recognized m5C modifications in CHD3 mRNA and maintained mRNA stability by recruiting PABPC1 protein. This regulatory process enhanced chromatin accessibility and improved the efficiency of homologous recombination (HR) repair, facilitating tumor cells to withstand platinum-induced apoptotic stress. In addition, SU056, an inhibitor of YBX1, exhibited the potential to reverse platinum resistance in subcutaneous and PDO orthotopic xenograft models. In conclusion, YBX1 is critical for ovarian cancer cells to alleviate the platinum-induced stress and may be a potential target for reversing drug-resistant therapies.
The introduction of PARP inhibitors (PARPis) and immune checkpoint inhibitors (ICIs) has marked a significant shift in the treatment landscape for solid tumors. Emerging preclinical evidence and initial clinical trials have indicated that the synergistic application of PARPis and ICIs may enhance treatment efficacy and potentially improve long-term patient outcomes. Nonetheless, how to identify specific tumor types and molecular subgroups most likely to benefit from this combination remains an area of ongoing research. This review thoroughly examines current studies on the co-administration of PARPis and ICIs across various solid tumors. It explores the underlying mechanisms of action, evaluates clinical efficacy, identifies potential responder populations, and delineates common adverse events alongside strategic management approaches. The aim is to offer a detailed understanding of this combination therapy, potentially guiding future therapeutic strategies for solid tumors.
Rationale: Trousseau syndrome is known as patients with tumors have a combination of multiple thrombi with systemic organ infarction. The incidence of ovarian clear cell cancer associated with Trousseau syndrome is relatively low. We report the case of a 41-year-old woman diagnosed with ovarian clear cell cancer with deep vein thrombosis and cerebral infarction who had a poor prognosis. Patient concerns: A 41-year-old woman was brought to our hospital with abdominal pain. Abdominal computerized tomography scan suggested large mass of ovarian origin which was considered an ovarian tumor with pelvic metastasis and peritoneal metastasis. Laboratory analyses indicated an elevated levels of serum tumor marker carbohydrate antigen 125 was 321.9 U/mL and the level of D-dimer was 16.71 mg/L. Diagnosis: The patient underwent pelvic mass aspiration was diagnosed with ovarian clear cell cancer. B-ultrasound revealed thrombosis of the lower limbs. Interventions: She underwent 2 neoadjuvant chemotherapies, along with anticoagulation therapy. However, it had a poor therapeutic effect, and the patient suffered from acute cerebral infarction that worsened. Outcomes: Chemotherapy and anticoagulation failed to stop the tumor and blood clot progression. The patient died 2 months after cerebral infarction without surgical treatment. Lessons: Gynecologists should be aware of the need for clinical suspicion of the risk of thrombosis during the treatment period of ovarian cancer and make careful decisions
Olaparib showed good efficacy and tolerability in the maintenance treatment of patients with initial therapy or high-grade serous recurrent ovarian cancer patients. This study aimed to analyze adverse events (AEs) of patients taking Olaparib and the quality of life (QoL) with Olaparib in 1 center of China. The study included 98 patients who received Olaparib and 210 patients without Olaparib from July 2018 to October 2021 for high-grade serous ovarian cancer in the Gynecology Oncology Department of Jiangsu Provincial Hospital. Information of clinicopathologic characteristics was collected from medical records. Then, we used the QLQ-C30 and Quality of Life Ovarian Cancer 28 Questionnaire (QLQ-OV28) to determine the QoL of 98 patients with and 210 patients without Olaparib. Among all 98 patients with Olaparib, 66 patients in first-line and 32 patients in more than second-line treatment. Regarding the best objective response with Olaparib maintenance in 78 patients with partial remission from most recent chemotherapy, 3 (3.84%) patients showed complete response (CR) and 6 (7.69%) showed as partial response (PR), whereas stable disease was observed in 42 patients (53.84%) and 27 patients (34.6%) showed as progression disease. AEs of Grade 3 and more were: anemia in 16 patients (16.32%), neutropenia in 20 patients (20.40%), thrombocytopenia in 4 patients (4.08%), and headache in 4 patients (4.08%). Dose reduction and drug discontinuation accounted for 73.40% and 20.40%, respectively. Olaparib as maintenance therapy increased QoL on all functioning domains and several symptom domains. Consistent with previous clinical trials, Olaparib maintenance therapy was proved safe and effective. Most patients may experience Grade 1 and 2 AEs. Olaparib maintenance therapy can increase QoL in several domains.