Spherical cancer models in tumor biology.

High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.

/pdf/rethinking-ovarian-cancer-ii-reducing-mortality-from-high-43u6pur2b0.pdf

Rethinking ovarian cancer II: Reducing mortality from high-grade serous ovarian cancer

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.

https://ijgc.bmj.com/content/ijgc/31/1/12.full.pdf

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.

https://ejmcm.com/article_1037_557a4ffed141d154066ba08c3bc4f683.pdf

Animal models in translational medicine: Validation and prediction

Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid light chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.

/pdf/systemic-immunoglobulin-light-chain-amyloidosis-40f5hysmuc.pdf

Systemic immunoglobulin light chain amyloidosis.

Ovarian cancer tumorgraft: Viral latency propagates lymphoma

Radical Extirpation With Intraoperative Radiotherapy for Locally Recurrent Gynecologic Cancer: An Institutional Review

https://academic.oup.com/annonc/article-pdf/24/suppl_1/i16/6674084/mdt042.51.pdf

L11.04ovarian avatar models predictive of platinum response in ovarian cancer patients

Background Increased immune infiltration in ovarian tumors has been linked to improved patient outcome. Nonetheless, responses to checkpoint blockade therapies have been disappointing in ovarian cancer patients. This has been attributed to the low mutational burden present in ovarian tumors. However, many tumor antigens have been identified in ovarian cancer, which underscores the critical need to identify new treatment strategies that will trigger anti-tumor immunity in ovarian cancer. Recent studies have revealed that defects in DNA damage repair (DDR) pathways can contribute to improved responses to immune-directed therapies.1 2 We previously discovered that CT45 expression sensitizes ovarian cancer cells to chemotherapy via its interaction with the protein phosphatase 4 (PP4) complex.3 PP4 is known to play a key role in DDR pathways; however, its potential effects on anti-tumor immunity remain unknown. Methods Using fostriecin, a commercially available inhibitor of PP4, we studied the effect of fostriecin on chemosensitivity using cell cycle analysis and cell viability assays. To study the effect of fostriecin on DNA damage, we performed comet assays and measured micronuclei along with FANCD2 foci formation. Furthermore, using western blot, qPCR, and T cell activation assays, we assessed the role of fostriecin in promoting an inflammatory response. We tested the efficacy of combining fostriecin with carboplatin and PD-1 inhibition in a syngeneic mouse model of ovarian cancer. Results Our results show that fostriecin treatment combined with carboplatin leads to increased carboplatin sensitivity, DNA damage, and micronuclei formation. Using a panel of ovarian cancer cells, we show that fostriecin treatment triggers an anti-tumor immune response via STAT1 activation resulting in increased expression of pro-inflammatory cytokines. Furthermore, in a syngeneic mouse ID8 ovarian cancer cell line, we demonstrate that combination treatment of fostriecin and carboplatin significantly increased CD8 T cell activation over carboplatin treatment alone. Conclusions Our work has identified a role for PP4 inhibition in promoting anti-tumor immunity. These findings form the groundwork for the rationale design of a clinical trial combining PP4 inhibitors with chemo-immunotherapy as a new approach in ovarian cancer treatment. References Rodier F, Coppe J-P, Patil CK, Hoeijmakers WAM, Munoz DP, Raza SR, et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nature Cell Biology 2009; 11: 973–979. Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, et al. CDK7 Inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer. Cancer cell 2020;37:37–54.e39. Coscia F, Lengyel E, Duraiswamy J, Ashcroft B, Bassani-Sternberg M, Wierer M, et al. Multi-level proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell 2018;175:159–170.e116.

https://jitc.bmj.com/content/jitc/8/Suppl_3/A337.2.full.pdf

559 Fostriecin potentiates genome instability and anti-tumor immunity in ovarian cancer

The Implementation Of Robotic-Assisted Surgery For Endometrial Cancer In The United States Lead To An Improvement Of Overall 30-Day Surgical Outcomes Without Increasing Costs: Is Technology Finally Allowing The Diffusion Of Minimally Invasive Surgery At A National Level?

Kristina A. Butler

Papers

Ovarian cancer tumorgraft: Viral latency propagates lymphoma

Radical Extirpation With Intraoperative Radiotherapy for Locally Recurrent Gynecologic Cancer: An Institutional Review

L11.04ovarian avatar models predictive of platinum response in ovarian cancer patients

559 Fostriecin potentiates genome instability and anti-tumor immunity in ovarian cancer

The Implementation Of Robotic-Assisted Surgery For Endometrial Cancer In The United States Lead To An Improvement Of Overall 30-Day Surgical Outcomes Without Increasing Costs: Is Technology Finally Allowing The Diffusion Of Minimally Invasive Surgery At A National Level?