PARP Inhibitors in Gynecologic Cancers: What Is the Next Big Development?

AbstractPurpose of ReviewConventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy.Recent FindingsPARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15 –30% of women with ovarian cancer will have a germline or somaticBRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand.SummaryWhile the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research

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Abstract Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up-regulated in four gynaecolo...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical exp...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research
The role of the immune system in the development of cancer has been a subject of ongoing clinical investigation in recent years. Emerging data demonstrate that tumorigenesis resulting in ovarian, uterine, and cervical cancers is a consequence of impaired host immune responses to cancerous cells. Leveraging the immune system through the use of immune checkpoint inhibitors, therapeutic vaccine therapy, and adoptive cell transfer presents a profound opportunity to revolutionize cancer treatment. This review will encompass the role of the immune system in development of gynecologic cancers and highlight recent data regarding i...
Source: Clinical Obstetrics and Gynecology - Category: OBGYN Tags: New and Novel Treatments for Gynecologic Cancer Source Type: research
We report a unique case of a 60-year-old woman developing endometrial cancer in a uterine deposit 18 years after she had undergone laparoscopic subtotal hysterectomy with morcellation for benign pathology. She had used unopposed estrogen as menopausal hormone therapy. She presented with a pelvic mass that was causing pressure symptoms. On imaging, the mass had an enhancing vascular nodular component and appeared to abut normal ovaries and the residual cervix. She proceeded to laparotomy, where a 12 cm pelvic mass was found morbidly adherent to the bladder anteriorly and to the cervical stump. The pelvic mass was excise...
Source: Case Reports in Womens Health - Category: OBGYN Source Type: research
Gynecologic cancers are the leading cause of cancer deaths in women worldwide, with annual diagnoses and deaths estimated at 90,000 and 30,000 in the United States, respectively [1]. Gynecologic cancers arise from similar cell/embryonic origins and share a variety of characteristics, but they are also unique in their own ways [2,3,4]. Five types of gynecologic cancers – cervical, ovarian, uterine, vaginal, vulvar – represent the vast majority of cases [5]. Ovarian cancer is the eighth most common cancer diagnosed and accounts for 5% of cancer deaths among women in the US, more than any other gynecologic cancer [6,7].
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Abstract Multiple practice changing studies were presented at the 2019 ESMO Congress in Barcelona, Spain. The ovarian cancer studies presented at the Presidential session will likely refine and redefine the initial treatment of ovarian cancer. Other compelling trial data in ovarian, uterine and cervical cancer were also unveiled. The key oral abstracts from this meeting are summarized in this meeting report. PMID: 31911006 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
ConclusionsIn this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Authors: Zhang X, Wang Y Abstract Gynecological cancer is the leading cause of cancer mortality in women. However, the mechanisms underlying gynecological cancer progression have remained largely unclear. In the present study, 799 dysregulated genes were identified in ovarian serous cystadenocarcinoma (OV), 488 dysregulated genes in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and 621 dysregulated genes in uterine corpus endometrial carcinoma (UCEC). Bioinformatics analysis revealed that mRNA splicing and cell proliferation-associated biological processes served important roles in OV pro...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
CONCLUSIONS: Gynecologic cancer has significant impacts on physical and mental aspects of HRQOL in older women. Interventions are needed to reduce pain, provide support, and prepare patients for changes in functioning and health. PMID: 31806400 [PubMed - as supplied by publisher]
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
AbstractTo determine the location patterns of distant metastases at initial staging and outcomes of ovarian, uterine, and cervical cancer patients. Data were obtained from the SEER database from 2010 to 2015. Analyses were performed using Kaplan –Meier and multivariate Cox proportional hazard methods. Of 3035 patients (median age: 63, range: 17–95) with stage IV gynecologic cancer, ovarian, uterine, and cervical cancers were present in 42%, 40%, and 18% of the cohort. The proportion of lung, liver, bone and brain metastases were identif ied in 38%, 57%, 4%, and 1% of ovarian cancer patients, 62%, 22%, 13%, and ...
Source: Clinical and Experimental Metastasis - Category: Cancer & Oncology Source Type: research
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