scholarly journals EPV279/#351 EPIK-O/ENGOT-OV61: a phase 3, randomized study of alpelisib + olaparib in patients with no germline brca mutation detected, platinum-resistant or -refractory, high-grade serous ovarian cancer

Author(s):  
P Konstantinopoulos ◽  
A González-Martín ◽  
F Cruz ◽  
M Friedlander ◽  
R Glasspool ◽  
...  
Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 55
Author(s):  
Francesco Plotti ◽  
Corrado Terranova ◽  
Federica Guzzo ◽  
Carlo De Cicco Nardone ◽  
Daniela Luvero ◽  
...  

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.


Radiology ◽  
2017 ◽  
Vol 285 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Mithat Gönen ◽  
Debra A. Goldman ◽  
Maura Miccò ◽  
...  

Author(s):  
Concetta Russo Spena ◽  
Lucia De Stefano ◽  
Barbara Salis ◽  
Carlotta Granchi ◽  
Maguie El Boustani ◽  
...  

Author(s):  
John Paul Shen ◽  
Ana Bojorquez-Gomez ◽  
Justin Huang ◽  
Matan Hofree ◽  
Kristin Klepper ◽  
...  

2017 ◽  
Vol 9 (8) ◽  
pp. 519-531 ◽  
Author(s):  
Robert T. Neff ◽  
Leigha Senter ◽  
Ritu Salani

Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes, the most common of which is high-grade serous ovarian cancer (HGSOC). Still today, ovarian cancer is primarily treated with chemotherapy and surgery. Recent advances in the hereditary understanding of this disease have shown a significant role for the BRCA gene. While only a minority of patients with HGSOC will have a germline BRCA mutation, many others may have tumor genetic aberrations within BRCA or other homologous recombination proteins. Genetic screening for these BRCA mutations has allowed improved preventative measures and therapeutic development. This review focuses on the understanding of BRCA mutations and their relationship with ovarian cancer development, as well as future therapeutic targets.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wenwen Guo ◽  
Xue He ◽  
Jing Ni ◽  
Liya Ma ◽  
Xianzhong Cheng ◽  
...  

This study aims to identify differentially expressed proteins related with platinum sensitivity and to find biomarkers for predicting platinum response and survival outcomes in patients with high-grade serous ovarian cancer (HGSOC). Eligible HGSOC patients were divided into platinum-sensitive and platinum-resistant groups according to platinum-free interval (PFI). Tissue protein lysates from tumor tissues were subjected to an in-solution tryptic digest followed by tandem mass tag (TMT) labeling of the resulting peptides and mass spectrometric analysis. Candidate proteins were identified using differentially expressed protein and gene set enrichment analysis (GSEA) and confirmed by immunohistochemistry (IHC), and their survival relevance was evaluated in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. The results showed that there was a significant difference in the protein expression profiling between the two patient groups. In the GSEA model, a gene set of 239 extracellular matrix (ECM)-related proteins was significantly enriched in the platinum-sensitive group [normalized enrichment score (NES) = 3.82, q &lt; 10−5], and this finding was confirmed in TCGA ovarian cancer cohort. Interestingly, an ECM-related gene expression, serpin family A member 10 (SERPINA10), was identified to be significantly positively correlated with overall survival (OS) and progression-free survival (PFS) in TCGA ovarian cancer cohort (all p &lt; 0.05). IHC results demonstrated that HGSOC patients with high SERPINA10 expression had longer PFI than the patients with low SERPINA10 expression (9 vs. 5 months, p = 0.038), and the SERPINA10 expression had an area under the receiver operating characteristic curve (AUC) value of 0.758 (95% CI = 0.612–0.905; p = 0.005) to discriminate the platinum-sensitive group from the platinum-resistant group. In conclusion, the results suggested that SERPINA10 could be a promising biomarker for predicting the response and survival in platinum-based chemotherapy of HGSOC.


2018 ◽  
Vol 44 (6) ◽  
pp. 2040-2047 ◽  
Author(s):  
Andreas Meier ◽  
Harini Veeraraghavan ◽  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Ramon Sosa ◽  
...  

2021 ◽  
Vol 162 ◽  
pp. S130-S131
Author(s):  
Logan Corey ◽  
Ayesha Alvero ◽  
Nivedita Tiwari ◽  
Yuan You ◽  
Ramandeep Rattan ◽  
...  

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