Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials

George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O.; Bowen, Rebecca; Michalarea, Vasiliki; Hagen, Tom van; Wong, Mabel; Rallis, Grigorios; Molife, L. Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana; Gore, Martin; Bono, Johann S. de; Kaye, Stan B.; Yap, Timothy A.

doi:10.1016/j.ejca.2017.01.020

Cited by 10 publications

(12 citation statements)

References 35 publications

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“…Baseline factors that may affect outcomes of patients with newly diagnosed advanced OC include tumor response (complete response [CR] v partial response [PR]) after platinum-based chemotherapy, BRCA mutation status, and timing of cytoreductive surgery (interval v upfront), as well as outcomes after surgery (residual v no gross residual disease). 15,16 Surgical outcome has been reported as 1 of the most important independent prognostic factors for survival, 16 with a significant survival advantage observed in patients with no gross residual disease compared with those with residual tumor burden of 1 to 10 mm or . 10 mm in diameter.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

DiSilvestro

Colombo

Scambia

et al. 2020

JCO

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PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status ( BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

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Section: Introductionmentioning

confidence: 99%

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

DiSilvestro

Colombo

Scambia

et al. 2020

JCO

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“…The standard treatment is platinum (Pt)‐based chemotherapy and surgical debulking of the tumour . There is a high proportion (~70%) of advanced‐stage cases at diagnosis, and the 5‐year overall survival rate is less than 40% across all stages . Ovarian cancer overall comprises a variety of tumour types with different histopathological features and biological behaviors .…”

Section: Introductionmentioning

confidence: 99%

“…3,4 There is a high proportion (~70%) of advanced-stage cases at diagnosis, and the 5-year overall survival rate is less than 40% across all stages. 5,6 Ovarian cancer overall comprises a variety of tumour types with different histopathological features and biological behaviors. 1,7 Although most ovarian cancer patients present with advanced-stage disease, response to front-line Pt-based chemotherapy is high, of the order of 75%.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the CSF‐1 receptor sensitizes ovarian cancer cells to cisplatin

Jin

et al. 2018

Cell Biochemistry & Function

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Ovarian cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely used in locally advanced ovarian cancer patients. Acquired or de novo cisplatin resistance remains the barrier to patient survival, and the mechanisms of cisplatin resistance are still not well understood. In the current study, we found that colony-stimulating-factor-1 receptor (CSF-1R) was upregulated in cisplatin-resistant SK-OV-3 and CaoV-3 cells. Colony-stimulating-factor-1 receptor knockdown suppressed proliferation and enhanced apoptosis in cisplatin-resistant SK-OV-3 and CaoV-3 cells. However, CSF-1R overexpression had inverse effects. While parental SK-OV-3 and CaoV-3 cells were more resistant to cisplatin after CSF-1R overexpression, CSF-1R knockdown in SK-OV-3 and CaoV-3 cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that CSF-1R significantly promoted active AKT and ERK1/2 signalling pathways in cisplatin-resistant cells. Furthermore, a combination of cisplatin and CSF-1R inhibitor effectively inhibited tumour growth in xenografts. Taken together, our results provide the first evidence that CSF-1R inhibition can sensitize cisplatin-refractory ovarian cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumours.

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“…We refer to this phenomenon as the "dual function" of KBTBD8, and some crucial proteins are known to function similarly. For example, BRCA1 mutations are well-known to be frequently linked with the occurrence of human ovarian cancer (Titus et al 2013 ; Hoskins and Gotlieb 2017 ; George et al 2017 ; Li et al 2016 ). BRCA1 is also required for DNA double-strand break (DSB) repair, and a BRCA1 deficiency in female mice results in increased oocyte apoptosis, which favors decreased primordial follicle reserve and impaired fertility (Hoskins and Gotlieb 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although the incidence of ovarian malignancy, mostly epithelial ovarian cancer (EOC), ranks third overall, the mortality rate in EOC patients is the highest among all types of gynecologic tumors (Bray et al 2018 ; Smith et al 2018 ; Torre et al 2018 ; Chen et al 2016 ; Matulonis et al 2016 ). An unfortunate impediment to the successful treatment of patients with advanced ovarian cancer (AOC) is the inevitable drug resistance to conventional anticancer therapies (Pistollato et al 2017 ; George et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression

et al. 2020

Mol Med

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Objectives Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. Methods We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. Results First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. Conclusion Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.

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Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials

Abstract: ABSTRACT

Cited by 10 publications

References 35 publications

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

Inhibition of the CSF‐1 receptor sensitizes ovarian cancer cells to cisplatin

Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression

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