The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1)

Murakami, Ryusuke; Matsumura, Noriomi; Michimae, Hirofumi; Tanabe, Hiroshi; Yunokawa, Mayu; Iwase, Haruko; Sasagawa, M; Nakamura, Toshiaki; Tokuyama, Osamu; Takano, Masashi; Sugiyama, Toru; Sawasaki, Takashi; Isonishi, Seiji; Takehara, Kazuhiro; Okamoto, Aikou; Mandai, Masaki; Konishi, Ikuo

doi:10.1016/j.ygyno.2019.02.010

Cited by 19 publications

(17 citation statements)

References 34 publications

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“…Because previous clinical trials of DD versus Q3W paclitaxel dosing for ovarian cancer did not report outcomes according to biomarker status [ 7 – 9 ], further studies are warranted to understand if specific subgroups of patients will benefit from DD paclitaxel dosing, particularly those with platinum-resistant and/or HRP ovarian cancer. JGOG2016A1, which was a survey study of JGOG3016, explored the efficacy of DD paclitaxel by histological subtype of high-grade serous carcinoma, and identified subgroups that were sensitive to DD regimen and subgroups that were less sensitive [ 31 ]. The correlation between these histological subtypes and BRCA /HRD status has not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial

Aghajanian

Swisher

Okamoto

et al. 2022

Gynecologic Oncology

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Weekly (compared to every 3 weeks) paclitaxel was associated with longer PFS in HRP and BRCAwt cohorts • PFS was improved with veliparib compared with control regardless of paclitaxel dosing schedule • In general, grade 3/4 adverse events were more common in dose-dense paclitaxel groups compared with every-3-week paclitaxel • Germline BRCA status showed no impact on incidences of adverse events across arms

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Section: Discussionmentioning

confidence: 99%

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial

Aghajanian

Swisher

Okamoto

et al. 2022

Gynecologic Oncology

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“…Tissue classified as solid and proliferative subtype exhibited significantly higher MYBL2 expression as compared with the papilloglandular subtype ( Figures 3A-C). The solid and proliferative subtype was previously not found to have a significant overlap in gene expression signature with the TCGA transcriptional subtypes and had no impact on overall survival (17,23). MYBL2 was highly expressed in the proliferative transcriptional subtype (Figures 2A,B) as well as tumors with morphological features consistent with cell proliferation (solid and proliferative histological subtype) (Figures 3B,C).…”

Section: Mybl2 Is Highly Expressed In the Majority Of Hgsoc Cases Andmentioning

confidence: 86%

Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples

et al. 2021

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Cell cycle control drives cancer progression and treatment response in high grade serous ovarian carcinoma (HGSOC). MYBL2 (encoding B-Myb), an oncogene with prognostic significance in several cancers, is highly expressed in most HGSOC cases; however, the clinical significance of B-Myb in this disease has not been well-characterized. B-Myb is associated with cell proliferation through formation of the MMB (Myb and MuvB core) protein complex required for transcription of mitotic genes. High B-Myb expression disrupts the formation of another transcriptional cell cycle regulatory complex involving the MuvB core, DREAM (DP, RB-like, E2F, and MuvB), in human cell lines. DREAM coordinates cell cycle dependent gene expression by repressing over 800 cell cycle genes in G0/G1. Here, we take a bioinformatics approach to further evaluate the effect of B-Myb expression on DREAM target genes in HGSOC and validate our cellular model with clinical specimens. We show that MYBL2 is highly expressed in HGSOC and correlates with expression of DREAM and MMB target genes in both The Cancer Genome Atlas (TCGA) as well as independent analyses of HGSOC primary tumors (N = 52). High B-Myb expression was also associated with poor overall survival in the TCGA cohort and analysis by a DREAM target gene expression signature yielded a negative impact on survival. Together, our data support the conclusion that high expression of MYBL2 is associated with deregulation of DREAM/MMB-mediated cell cycle gene expression programs in HGSOC and may serve as a prognostic factor independent of its cell cycle role. This provides rationale for further, larger scale studies aimed to determine the clinical predictive value of the B-Myb gene expression signature for treatment response as well as patient outcomes.

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“…HGSC is not a single disease but a group of neoplasms that include different transcriptional subtypes and different histopathological subtypes [21,127]. FTE-derived HGSC metastasizes rapidly and OSE-derived HGSC has longer latency, lower penetrance, and a worse prognosis [35,36].…”

Section: Discussionmentioning

confidence: 99%

Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding

Otsuka

Matsuura

2020

Diagnostics

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High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian carcinoma. Many HGSCs are now believed to originate in the fallopian tube epithelium; ovarian surface epithelium is another possible origin. Thus, current screening methods, i.e., ultrasonography and serum CA-125 measurements, have a limitation in their early detection. Recently, circulating biomarkers, such as tumor DNA, autoantibody, and microRNA, have been investigated to detect HGSCs. As cancer cells in the fallopian tube flow into the endometrial cavity, the detection of exfoliated cells, tumor DNA, and proteome from samples obtained from the endometrial cavity or the cervix may be useful. The risk of ovarian serous carcinoma is affected by the use of oral contraceptive and menopausal hormone therapy (MHT). MHT regimens causing endometrial bleeding increase serous carcinoma risk, hence, incessant retrograde bleeding from the endometrial cavity into the Douglas pouch appears to play an important role in high-grade serous carcinogenesis. In this review, we provide an overview of current and novel screening methods and prevention approaches for ovarian and fallopian tube HGSC.

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The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1)

Cited by 19 publications

References 34 publications

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial

Oncogenic B-Myb Is Associated With Deregulation of the DREAM-Mediated Cell Cycle Gene Expression Program in High Grade Serous Ovarian Carcinoma Clinical Tumor Samples

Screening and Prevention for High-Grade Serous Carcinoma of the Ovary Based on Carcinogenesis—Fallopian Tube- and Ovarian-Derived Tumors and Incessant Retrograde Bleeding

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