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BRCA Mutation and PARP Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Arjun Mittra, James H. Doroshow, Alice P. Chen
Rucaparib was the first PARP inhibitor studied clinically. Preclinical data in ovarian cancer cell lines was encouraging for the single agent and in combination with carboplatin, doxorubicin, gemcitabine, paclitaxel and topotecan. The BRCA status of these cell lines was not reported; it was suggested that the activity of rucaparib in ovarian cancer was not confined to BRCA-mutated tumors or high-grade serous carcinoma [53].
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Robert D. Morgan, Andrew R. Clamp, Gordon C. Jayson
Epithelial ovarian cancer can be classified into five main histological subtypes: high-grade serous, low-grade serous, endometrioid, clear cell and mucinous carcinoma. High-grade serous carcinoma is the commonest form of epithelial ovarian cancer, accounting for approximately 80% of all cases.
Histopathological aspects of peritoneal malignancy
Published in Tom Cecil, John Bunni, Akash Mehta, A Practical Guide to Peritoneal Malignancy, 2019
Babatunde Rowaiye, Norman Carr
Ovarian serous borderline tumours and low-grade serous carcinoma share many characteristics and are histologically and biologically distinct from high-grade serous carcinoma [56]. They present at a relatively young age, and there is usually prolonged survival, although the tumours are relatively resistant to chemotherapy. They also show a different pattern of genetic alterations; for example, they generally lack TP53 mutations [56]. It has been proposed that they may arise from papillary tubal hyperplasia [57].
Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression
Published in OncoImmunology, 2022
Tatiana V. Kudling, James H.A. Clubb, Dafne C.A. Quixabeira, Joao M. Santos, Riikka Havunen, Alexander Kononov, Camilla Heiniö, Victor Cervera-Carrascon, Santeri Pakola, Saru Basnet, Susanna Grönberg-Vähä-Koskela, Victor Arias, Ivan Gladwyn-Ng, Katri Aro, Leif Bäck, Jari Räsänen, Ilkka Ilonen, Kristian Borenius, Mikko Räsänen, Otto Hemminki, Antti Rannikko, Anna Kanerva, Johanna Tapper, Akseli Hemminki
Since the reagents and assays for hamsters and immunodeficient animals are limited, and there is a point in studying the hypothesis from a translational perspective, we continued with ex vivo samples obtained from ovarian cancer patients. We first focused on the samples of high-grade serous carcinoma, which make up the majority of epithelial ovarian cancer cases.27 Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival is 42% and 26%, respectively.28 Standard therapy includes surgery followed by platinum-based chemotherapy, however, to date, several immunotherapy approaches have been considered as a potential ovarian cancer treatment.29 The reason might be that epithelial ovarian cancers usually have high frequency of T cell infiltrates, but also high percentage of immunosuppressive cells, such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs).29,30 Thus, converting tumor microenvironment toward immunostimulatory one with an IL7 coding virus might be required to improve patients’ response rate and overall survival.
The predictive role of thrombocytosis in benign, borderline and malignant ovarian tumors
Published in Platelets, 2020
Ganiy Opeyemi Abdulrahman, Nagindra Das, K Lutchman Singh
High grade serous carcinoma is the commonest pathological sub-group of ovarian cancer, and it is often diagnosed at Stage III or IV with 5-year survival for women being 42% and 26%, respectively [3]. In the UK, most women would either present to their general practitioner in the first instance or the pelvic mass would be found incidentally during physical examination or radiological investigations in secondary/tertiary care settings. Although CA-125 is usually measured in women with suspicious pelvic mass, it is not without its own deficiencies as a screening test. It is estimated that CA-125 only has a positive predictive value (PPV) of 69%, although a higher negative predictive value (NPV) of 88% for the detection of ovarian cancer [4]. CA-125 has also been reported to be raised in benign ovarian tumors. Chen and colleagues report as high a false-positive rate as 40% in patients with benign disease [5]. CA-125 has been reported to be raised in pregnancy [6], menstruation [7], endometriosis [8], and even in a case of a male patient with myeloma [9]. It is therefore essential that new diagnostic markers are identified to either complement or replace CA-125 altogether.
Prognosis of ovarian cancer is associated with effector memory CD8+ T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells
Published in OncoImmunology, 2018
Sonja Lieber, Silke Reinartz, Hartmann Raifer, Florian Finkernagel, Tobias Dreyer, Holger Bronger, Julia M. Jansen, Uwe Wagner, Thomas Worzfeld, Rolf Müller, Magdalena Huber
Ovarian cancer is the most lethal gynecological malignancy with an overall 5-year survival rate of approximately 40%.1 The high grade serous carcinoma subtype represents the most common and aggressive subtype of ovarian cancer entities. As in many other malignancies, its tumor microenvironment (TME) plays a pivotal role in disease progression. A characteristic feature of the ovarian TME is its composition of anatomically and functionally different compartments, including tumor tissue, invaded host tissues (in particular the omentum) and the peritoneal fluid, which at advanced stages occurs as a malignancy-associated peritoneal effusion, termed ascites.2–5 Besides cytokines, growth factors, lipids and other soluble mediators this effusion contains large numbers of immune cells and tumor cell spheroids with “stem-like” properties that are likely to play a pivotal role in transcoelomic metastasis and chemotherapy failure.6 The most common cell types in ovarian cancer ascites are macrophages and CD8+ T cells that are immunosuppressed by the TME and programmed to exert pro-tumorigenic functions.2–5 Understanding the molecular mechanisms underlying these defects in immune surveillance is key to the development of efficient immune therapies targeting the pro-metastatic and resistance-promoting detached tumor cells and spheroids in the peritoneal fluid of ovarian cancer.