EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner.

Poly ADP-ribose polymerase inhibitors (PARPi) are first-line maintenance therapy for ovarian cancer and an alternative therapy for several other cancer types. However, PARPi-resistance is rising, and there is currently an unmet need to combat PARPi-resistant tumors. Here, we created an immunocompetent, PARPi-resistant mouse model to test the efficacy of combinatory PARPi and euchromatic histone methyltransferase 1/2 inhibitor (EHMTi) in the treatment of PARPi-resistant ovarian cancer.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro.

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

Background: Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery.

Methods: The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of Poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers Euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory dsRNA formation and elicits several immune signaling pathways in vitro.

Ovarian cancer think tank: An overview of the current status of ovarian cancer screening and recommendations for future directions.

Early diagnosis and screening of ovarian cancer remain significant challenges to improving patient outcomes. There is an urgent need to implement both established and modern strategies to address the "early detection" conundrum, especially as new research continues to uncover the complexities of the disease. The discussion provided is the result of a unique research conference focused on reviewing early detection modalities and providing insight into future approaches.

A rare case of cardiac metastasis of squamous cell carcinoma of the cervix with a review of existing case reports and treatment modalities.

•Cardiac metastasis is a rare complication of squamous cell carcinoma of the cervix.•Biologic agents may be a useful treatment modality for cardiac metastasis of squamous cell carcinoma of the cervix.•Multidisciplinary approach is required to treat cardiac metastasis of squamous cell carcinoma of the cervix.

Cancer and the risk of perioperative arterial ischaemic events.

Background And Aims: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischaemic events.

Methods: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006 and 2016.

Prevention of venous thromboembolism in patients with cancer.

Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population.

Combinatory EHMT and PARP inhibition induces an interferon response and a CD8 T cell-dependent tumor regression in PARP inhibitor-resistant models.

Euchromatic histone lysine methyltransferases 1 and 2 (EHMT1/2), which catalyze demethylation of histone H3 lysine 9 (H3K9me2), contribute to tumorigenesis and therapy resistance through unknown mechanisms of action. In ovarian cancer, EHMT1/2 and H3K9me2 are directly linked to acquired resistance to poly-ADP-ribose polymerase (PARP) inhibitors and are correlated with poor clinical outcomes. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory inhibition of EHMT and PARP is effective in treating PARP inhibitor resistant ovarian cancers.

Utilizing preoperative arterial embolization to minimize blood loss at time of vulvar sarcoma resection: A case report.

Selective arterial embolization has long been utilized in the field of obstetrics and gynecology as both a prophylactic and therapeutic measure. We present a case of a highly vascularized, poorly differentiated, radiation-related vulvar sarcoma that was resected immediately following selective arterial embolization. Arterial embolization in patients with gynecologic malignancies has been shown to compromise blood supply to the tumor and decrease the risk of hemorrhage and related surgical complications.

Loss of Claudin-4 Reduces DNA Damage Repair and Increases Sensitivity to PARP Inhibitors.

High-grade serous ovarian cancer is the deadliest gynecologic malignancy due to progression to resistant disease. Claudin-4 is classically defined as a tight junction protein and is often associated with epithelial cancers. Claudin-4 is aberrantly expressed in nearly 70% of all ovarian cancer tumors and conveys a worse overall prognosis.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.

Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy.

Assessing Inequities in Cervical Cancer Quality of Care and Survival Related to Ethnicity and Socioeconomic Factors.

Objective: This study aimed to assess the effect that race and socioeconomic factors have on the provision of care to cervical cancer patients based on National Comprehensive Cancer Network (NCCN) recommended treatment guidelines.

Materials And Methods: To do this, we completed a retrospective cohort study using the American College of Surgeon's Nation Cancer Database from 2004 to 2016. We identified all reported cases of cervical cancer in that period.

Treatment of epithelial ovarian cancer.

Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

Objective: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data.

Adherence to postoperative thromboprophylactic medication among gynecologic oncology patients: A subanalysis.

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality among gynecologic cancer patients, especially in the immediate postoperative period. We sought to identify patterns related with patient non-adherence to postoperative prophylactic anticoagulation.

Methods: Participant data (N = 400) were reviewed from a previously conducted randomized controlled trial comparing the safety and efficacy of prophylactic postoperative anticoagulation with enoxaparin versus apixaban among gynecologic oncology patients.

Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial.

Importance: Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic.

Objective: To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer.

COVID-19 and ovarian cancer: Exploring alternatives to intravenous (IV) therapies.

• The pandemic COVID-19 requires alternative methods and thinking to keep healthcare professionals and patients safe. • In COVID-19 hot spots, oral therapies may be viable alternatives to intravenous therapies for treatment of ovarian cancer. • Minimizing patient visits to hospitals and cancer clinics may help mitigate the spread of SARS-CoV-2.

Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

Introduction: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab.

Methods: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240.

Results: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity).

African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type.

Objective: There has been an increase in the use of neoadjuvant chemotherapy in recent years. Our objective was to determine if African American women are more likely to receive neoadjuvant chemotherapy than primary debulking surgery, when compared to their Caucasian counterparts, and the impact of such an approach on oncologic outcomes.

Methods: A retrospective cohort study was performed using the National Cancer Database (NCDB).