Updates and New Options in Advanced Epithelial Ovarian Cancer Treatment

Kurnit, Katherine C.; Fleming, Gini F.; Lengyel, Ernst

doi:10.1097/aog.0000000000004173

Cited by 218 publications

(171 citation statements)

References 83 publications

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“…Standard systemic chemotherapy for OC includes a combination of carboplatin and paclitaxel, and since recently, PARP (poly ADP-ribose polymerase) inhibitors (Olaparib, niraparib) and anti-angiogenic agents (bevacizumab) have been introduced as first-line therapy [ 31 ]. Systemic therapy medications are associated with a potential risk of cardiovascular complications, referred to as cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus

et al. 2021

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Background: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival. Objectives: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer. Materials and methods: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II–IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52–129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan–Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy. Results: The Kaplan–Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005). Conclusions: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus

et al. 2021

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“…Epithelial ovarian cancer (OC) is one of the deadliest gynecological malignancies (12). Despite recent improvements in our understanding of OC biology (13) and the development of new treatments (14), the vast majority of women with advanced stage OC will experience recurrence and succumb to the disease. Most women develop resistance to platinum (Pt) chemotherapy, which is part of the standard first line treatment for OC (15).…”

Section: Introductionmentioning

confidence: 99%

The Ratio of Toxic-to-Nontoxic miRNAs Predicts Platinum Sensitivity in Ovarian Cancer

et al. 2021

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Ovarian cancer remains one of the deadliest gynecologic malignancies affecting women, and development of resistance to platinum remains a major barrier to achieving a cure. Multiple mechanisms have been identified to confer platinum resistance. Numerous microRNAs (miRNAs) have been linked to platinum sensitivity and resistance in ovarian cancer. miRNA activity occurs mainly when the guide strand of the miRNA, with its seed sequence at position 2-7/8, is loaded into the RNA-induced silencing (RISC) complex and targets complementary short seed matches in the 3' untranslated region of mRNAs. Toxic 6mer seeds, which target genes critical for cancer cell survival, have been found in tumor suppressive miRNAs. Many small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) can also kill cancer cells via toxic seeds, the most toxic of which carry G-rich 6mer seed sequences. We showed here that treatment of ovarian cancer cells with platinum led to increased RISC-bound miRNAs carrying toxic 6mer seeds and decreased miRNAs with nontoxic seeds. Platinum-tolerant cells did not exhibit this toxicity shift but retained sensitivity to cell death mediated by siRNAs carrying toxic 6mer seeds. Analysis of RISC-bound miRNAs in ovarian cancer patients revealed that the ratio between miRNAs with toxic versus nontoxic seeds was predictive of treatment outcome. Application of the 6mer seed toxicity concept to cancer relevant miRNAs provides a new framework for understanding and predicting cancer therapy responses.

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“…Ovarian cancer represents the gynecological malignancy responsible for the highest number of deaths each year in western countries [1]. Ovarian cancers are a heterogeneous group of tumors including separate entities and are divided into epithelial (about 90% of cases), germ cell (3%), and sex cord-stromal (2%) [2].…”

Section: Introduction 1epithelial Ovarian Cancermentioning

confidence: 99%

Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision

et al. 2021

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Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence.

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Updates and New Options in Advanced Epithelial Ovarian Cancer Treatment

Abstract: New data have emerged that can help guide decision making on the increasingly complex medical and surgical treatment options for women with ovarian cancer.

Cited by 218 publications

References 83 publications

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus

The Ratio of Toxic-to-Nontoxic miRNAs Predicts Platinum Sensitivity in Ovarian Cancer

Role of Circulating miRNAs in Therapeutic Response in Epithelial Ovarian Cancer: A Systematic Revision

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