Abstract：
:Ovarian, endometrial and cervical cancers are the most prevalent gynecologic cancers in the United States and account for significant mortality. Translational research into these cancers has highlighted the distinctive molecular and genomic profiles of these cancers finding that, even within a disease site, the landscapes and drivers of neoplasia are distinctive. Despite this molecular diversity, activation of the phosphatidylinositol-3-kinase (PI3K) pathway appears to be conserved in subsets of these tumors, suggesting that strategies that antagonize mediators in this signaling cascade could offer anti-tumor efficacy. Extensive pre-clinical and clinical data have demonstrated that single agent targeted therapies lead to modest single agent activity of generally limited duration, even in the setting of innate PI3K pathway activation via mutation or amplification. These findings in the laboratory and clinic have prompted investigations into resistance pathways following PI3K pathway inhibition in order to understand escape pathways and restore tumor cell sensitivity. A next generation of clinical trial investigations will focus on novel combinations in order to define how these important therapeutics can be used in the clinic. This review will present preclinical data that supports the role of the PI3K pathway in ovarian, endometrial and cervical cancers, in addition to discussing the reported clinical trial experience with PI3K pathway inhibition. A specific focus will be on the rationale behind ongoing clinical trials utilizing novel agents in concert with PI3K pathway inhibitors to reverse resistance in populations with and without gain of function alterations in this oncogenic signaling cascade.
journal_name
Gynecol Oncoljournal_title
Gynecologic oncologyauthors
Bregar AJ,Growdon WBdoi
10.1016/j.ygyno.2015.09.083subject
Has Abstractpub_date
2016-02-01 00:00:00pages
333-44issue
2eissn
0090-8258issn
1095-6859pii
S0090-8258(15)30144-Xjournal_volume
140pub_type
杂志文章,评审abstract：BACKGROUND:Improved treatment for advanced cervical cancer is needed; currently, treatment options include combined chemotherapy and bevacizumab or pembrolizumab monotherapy for PD-L1 positive disease. PIK3CA and KRAS mutations have been reported in cervical cancers; this study therefore tested dual inhibition of PI3K ...
journal_title：Gynecologic oncology
pub_type： 杂志文章,多中心研究
doi：10.1016/j.ygyno.2019.05.003
更新日期：2019-07-01 00:00:00
abstract：:Copyright ...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1997.4926
更新日期：1998-02-01 00:00:00
abstract：OBJECTIVES:The role of MDR1 in clinical paclitaxel resistance remains poorly characterized. This study sought to identify the incidence and significance of P-glycoprotein (P-gp) over-expression on survival, tumor response to paclitaxel and the effect of prior cytotoxic exposure on P-gp expression in patients with paire...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2003.11.053
更新日期：2004-04-01 00:00:00
abstract：:A retrospective analysis of 45 patients with epithelial ovarian carcinoma who underwent second-look procedure after initial cytoreduction and platinum-based combination chemotherapy was undertaken. Each patient was evaluated for the result of CA 125 after a third course of chemotherapy, the result of CA 125 prior to s...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1995.1121
更新日期：1995-05-01 00:00:00
abstract：:The existing means of detecting recurrent ovarian carcinoma are notoriously poor. Positron emission tomography (PET) is a form of computer-assisted imaging which produces images reflective of the biochemistry of the tissues rather than their physical characteristics. PET imaging with the positron emitting glucose anal...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1993.1268
更新日期：1993-11-01 00:00:00
abstract：OBJECTIVE:Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-tre...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2019.09.009
更新日期：2019-11-01 00:00:00
abstract：:Epithelial ovarian carcinoma consists of not one, but several, entities. A number of subtypes exist, including high-grade and low-grade serous carcinomas, clear cell, endometrioid carcinoma and mucinous carcinoma. Historically, women with epithelial ovarian cancer have been treated similarly and "lumped" in the same c...
journal_title：Gynecologic oncology
pub_type： 杂志文章,评审
doi：10.1016/j.ygyno.2014.11.078
更新日期：2015-02-01 00:00:00
abstract：OBJECTIVES:To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expres...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2020.08.026
更新日期：2020-11-01 00:00:00
abstract：BACKGROUND:We report an isolated recurrence at the residual cervix shortly after abdominal radical trachelectomy for cervical cancer. CASE:A 34-year-old woman underwent radical abdominal trachelectomy and pelvic lymphadenectomy for FIGO stage IB1 squamous cell cervical cancer. The tumor measured 10 mm in maximum diame...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2005.07.107
更新日期：2005-12-01 00:00:00
abstract：:Two cases of primary retroperitoneal mucinous cystoadenocarcinoma of the ovarian type are reported. Both tumors occurred in females with bilateral normal ovaries and contained benign, borderline, and malignant mucinous epithelium. Full-thickness infiltration of the cyst wall was not found. In addition to surgery, one ...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1994.1295
更新日期：1994-11-01 00:00:00
abstract：OBJECTIVE:The purpose of this phase II study was to evaluate on an intent-to-treat basis the activity and toxicity of single-agent vinorelbine (VRL) as second-line chemotherapy of patients with platinum-resistant ovarian cancer. Platinum-resistant disease was defined as disease refractory to or relapsing within 12 mont...
journal_title：Gynecologic oncology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1006/gyno.2000.6089
更新日期：2001-04-01 00:00:00
abstract：OBJECTIVES:We aimed to evaluate whether carboplatin has a comparable efficacy with cisplatin as part of weekly concurrent chemoradiotherapy for cervical cancer (Car-RT vs. Cis-RT). METHODS:A literature search was conducted and both prospective and retrospective studies that evaluated the efficacy of Car-RT for cervica...
journal_title：Gynecologic oncology
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.ygyno.2018.07.005
更新日期：2018-09-01 00:00:00
abstract：:Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenect...
journal_title：Gynecologic oncology
pub_type： 杂志文章,meta分析
doi：10.1016/j.ygyno.2019.03.254
更新日期：2019-06-01 00:00:00
abstract：OBJECTIVE:To evaluate the long-term outcomes of young early stage cervical cancer patients wishing to preserve their childbearing potential. METHODS:Data of young (aged <40 years) patients with early stage cervical cancer were prospectively collected. All patients with stage IA2, IB1 and IB2 cervical cancer were inclu...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2019.04.007
更新日期：2019-07-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to evaluate whether the results of the Hybrid Capture II (HCII) assay for detecting high-grade squamous intraepithelial lesions (H-SIL) or cervical carcinoma can be improved by increasing the relative light units (RLU) level. STUDY DESIGN:We included 2271 women (mean age 38.7 +/- 12....
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2005.07.011
更新日期：2005-11-01 00:00:00
abstract：OBJECTIVE:To evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for detecting recurrent epithelial ovarian cancer limited to retroperitoneal adenopathy. METHODS:Fourteen patients (median age = 53 years) with rising serum CA125 levels, and negative or equivocal conventional CT im...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2005.06.019
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:Imaging modalities to evaluate ovarian/fallopian tube cancer patients for recurrence are limited. Positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound lack the sensitivity to consistently detect recurrence or measurable disease in these patients. A new t...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.2002.6606
更新日期：2002-04-01 00:00:00
abstract：:Among 713 patients followed after treatment for cancer of the uterine cervix, 48 (6.6%) had a metastasis to the bone. The rates of metastasis in each of the four clinical stages were 11/273 (4.0%) in stage I, 16/243 (6.6%) in stage II, 13/162 (8.0%) in stage III, and 8/35 (22.9%) in stage IV, respectively. The most fr...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/0090-8258(89)90853-6
更新日期：1989-01-01 00:00:00
abstract：OBJECTIVE:To evaluate clinical outcomes of patients with BRCA-associated ovarian cancer who developed brain metastases (BM). METHODS:Patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and BM, treated at a single institution from 1/1/2008-7/1/2018, were identified from two institution...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2019.05.004
更新日期：2019-07-01 00:00:00
abstract：OBJECTIVES:Insomnia is common in women with ovarian cancer but there are limited prospective data on the frequency and degree of impact on patients. Our objective was to determine the prevalence of insomnia over the first three years after a diagnosis of ovarian cancer; and the relationship between insomnia and quality...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2020.06.500
更新日期：2020-09-01 00:00:00
abstract：OBJECTIVE:Hydroxysteroid-dehydrogenase-17b (HSD17b) genes control the last step in estrogen biosynthesis. The isoenzymes HSD17b2 and HSD17b4 in the uterus preferentially catalyze the conversion of estradiol, the most potent and active form of estrogen, to estrone, the inactive form of estrogen. Endometrial adenocarcino...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2010.11.014
更新日期：2011-04-01 00:00:00
abstract：OBJECTIVE:Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2018.12.019
更新日期：2019-03-01 00:00:00
abstract：BACKGROUND:Neuroendocrine carcinomas (NECs) of the cervix comprise only 2% of all cervical cancers. Prospective data is limited and treatment guidelines rely on retrospective reviews and literature from lung NEC. The objective of this study was to report our experience in the management of this rare disease. METHODS:T...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2013.01.014
更新日期：2013-04-01 00:00:00
abstract：OBJECTIVES:CD4(+)CD25(+) regulatory T-cells (Tregs), that express the transcription factor FOXP3, suppress effector T-cell populations and can enable tumour cells to evade the host immune response. In this study, we investigated the numbers of FOXP3(+) Tregs in the normal and malignat endometrium and examined potential...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2008.04.021
更新日期：2008-08-01 00:00:00
abstract：OBJECTIVE:A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with previously treated squamous cell carcinoma of the cervix. METHODS:Eligible patients were to have measurable disease and not more than one prior chemotherapy regimen that could include carboplatin or cisplatin but...
journal_title：Gynecologic oncology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/s0090-8258(03)00253-1
更新日期：2003-07-01 00:00:00
abstract：:Taxol is one of the more significant advances in cancer chemotherapy in the last 10-15 years with a 30-50% response rate in both breast and ovarian cancers. The toxicity profile of taxol is still evolving as changes in the dosing and scheduling of the drug are instituted. We herein present the first evidence of taxol-...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.1993.1287
更新日期：1993-11-01 00:00:00
abstract：:A patient with three synchronous, Stage I neoplasms of the ovary, kidney, and lung, who underwent resection of all lesions at the same operative procedure, is presented. The incidence of multiple primary malignancies and the prognosis for Stage I cancers of the ovary, kidney, and lung are reviewed. ...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/0090-8258(89)90615-x
更新日期：1989-04-01 00:00:00
abstract：BACKGROUND:High tumor dissemination (HTD) is a major risk factor for serious morbidity after primary ovarian cancer (OC) surgery, particularly in medically compromised patients. We performed a pilot study of whether CT findings could predict extent of disease and surgical complexity necessary in advanced OC. METHODS:P...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1016/j.ygyno.2013.05.007
更新日期：2013-08-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to determine the prevalence and types of complementary and alternative medicine (CAM) usage by women with gynecologic cancer in an outpatient midwestern university practice. METHODS:Any patient with a gynecologic cancer seen in the outpatient clinic of the gynecologic oncology divis...
journal_title：Gynecologic oncology
pub_type： 杂志文章
doi：10.1006/gyno.2001.6515
更新日期：2002-03-01 00:00:00
abstract：OBJECTIVE:To review and summarize evidence from clinical, translational and epidemiologic studies which have examined the clinically relevant aspects of HPV type prevalence and cervical dysplasia in HIV-infected women. METHODS:Relevant studies were identified through a MEDLINE search. References of identified reports ...
journal_title：Gynecologic oncology
pub_type： 杂志文章,评审
doi：10.1016/j.ygyno.2009.10.058
更新日期：2010-03-01 00:00:00
