MUS81 Participates in the Progression of Serous Ovarian Cancer Associated With Dysfunctional DNA Repair System

Conclusions: MUS81 is involved in the progression of SOC and inhibition of MUS81 could augment the susceptibility to chemotherapeutic agents. MUS81 might represent a novel molecular target for SOC chemotherapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Contributors : Philip C Schouten ; Daniel J Vis ; Ewald van Dijk ; Esther H Lips ; Esther Scheerman ; Carolien H van Deurzen ; Patricia C Ewing-Graham ; Agnes Jager ; Els M Berns ; Petra M Nederlof ; Lodewyk F Wessels ; Sabine C LinnSeries Type : Genome variation profiling by genome tiling arrayOrganism : Homo sapiensInactivating germline BRCA1 and BRCA2 mutations confer a defect in homologous recombination DNA repair which was found to leave traces in tumor DNA copy number aberration (CNA) profiles. In analogy to previously trained breast cancer CNA classifiers that predicted association with BRCA1 and BRCA2 mutated cance...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome variation profiling by genome tiling array Homo sapiens Source Type: research
nto Yu Yu Ovarian cancers remain one of the most common causes of gynecologic cancer-related death in women worldwide. The standard treatment comprises platinum-based chemotherapy, and most tumors develop resistance to therapeutic drugs. One mechanism of developing drug resistance is alterations of molecules involved in apoptosis, ultimately assisting in the cells’ capability to evade death. Thus, there is a need to focus on identifying potential drugs that restore apoptosis in cancer cells. Here, we discuss the major inducers of apoptosis mediated through various mechanisms and their usefulness as potentia...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of p...
Source: Clinical Epigenetics - Category: Research Authors: Tags: Research Source Type: research
CONCLUSIONS: Upfront knowledge of BRCA status is encouraged, given the recent advent of targeted therapies and for the decision regarding optimal sequence of available therapeutic strategies. PMID: 31646805 [PubMed - in process]
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
SummaryEpithelial ovarian cancer (EOC) accounts for nearly 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery and neo (adjuvant) platinum-based chemotherapy. Relapse of advanced high grade serous ovarian cancer (HGSOC) is related to the development of drug resistance. A defective DNA damage response is a defining hallmark of HGSOC. Poly (ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in breast cancer gene (BRCA1 orBRCA2) mutation carriers. Apart from inducing synthetic ...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
AbstractPARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer. The exact indications and study populations vary slightly between the di...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
Contributors : Lesley Conrad ; Ken Lin ; Tulip Nandu ; Bryan Gibson ; Ali Gazdar ; Jayanthi Lea ; W L KrausSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInhibitors of nuclear poly(ADP-ribose) polymerase (PARP) enzymes (e.g., PARP-1) have improved clinical outcomes in ovarian cancer, especially in patients with BRCA1/2 gene mutations or additional homologous recombination (HR) DNA repair pathway deficiencies. These defects serve as biomarkers for response to PARP inhibitors (PARPi). We sought to identify an additional biomarker that could predict responses to both conventional chemot...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
AbstractBackgroundPoly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair (DDR). DDR defects due to HRRm (eg BRCA mutation [BRCAm]) or resulting in HRD (eg global loss of heterozygosity) may sensitize tumors to PARP inhibitors, eg olaparib. Olaparib monotherapy has activity in BRCAm ovarian, breast, pancreatic, and prostate cancer, and in prostate cancer with DDR defects beyond BRCAm (TOPARP). Olaparib improved efficacy outcomes vs placebo/chemotherapy as treatment in  ≤ 3rd-line (3L) HER2-negative BRCAm breast cancer (OlympiAD) and ≥2L BRCAm ovarian cancer (SOLO3), and maintenance the...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
This study aims to summarize the indications and toxicity of PARP inhibitors, the mechanism of action, targeted treatment of drug resistance, and potential methods to manage drug-resistant diseases. We used the term "ovarian cancer" and the names of each PARP inhibitor as keywords to search articles published in the Medical Subject Headings (MeSH) on Pubmed, along with the keywords "clinicaltrials.gov" and "google.com/patents" as well as "uspto.gov." The FDA has approved olaparib, niraparib, and rucaparib for treatment of recurrent epithelial ovarian cancer (EOC). Talazoparib and vel...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
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