Abstract A25: Investigating the co-occurrence of potentially pathogenic DNA repair pathways alleles in BRCA1 or BRCA2 mutation carrier women with ovarian cancer.

Author(s):  
Wejdan M. Alenezi ◽  
Timothee Revil ◽  
Dunarel Badescu ◽  
Suzanna L. Arcand ◽  
Guy Rouleau ◽  
...  
2017 ◽  
Vol 10 (2) ◽  
pp. 433-437 ◽  
Author(s):  
María Jesús  Rubio Pérez

Introduction: The current standard of care for ovarian cancer is optimal cytoreduction with adjuvant chemotherapy based on a platinum/taxane combination. Although the response rate to this therapy is high, most patients ultimately relapse. Response to second-line therapy and prognosis are linked to the platinum-free interval (PFI); when both improve, the PFI increases. As a result, there is an increasing interest in the PFI extension strategies including platinum-free combinations. Case Presentation: A 50-year-old postmenopausal woman presented with ovarian serous carcinoma with peritoneal carcinomatosis. First-line neoadjuvant chemotherapy with carboplatin plus paclitaxel was initiated, followed by surgery and carboplatin plus paclitaxel chemotherapy. Eight months after the last cycle, CT revealed extensive supra- and infradiaphragmatic node involvement, and second-line chemotherapy was initiated with trabectedin and pegylated liposomal doxorubicin (PLD). Partial response was achieved and successfully maintained for 18 cycles. After the 18th cycle and a 25-month PFI, CT imaging evidenced disease progression. As the patient was a BRCA2 mutation carrier, third-line chemotherapy was initiated with carboplatin and gemcitabine every 3 weeks. After the third cycle, imaging confirmed complete response, which was maintained after the sixth and final cycle. Maintenance treatment with olaparib was initiated. At present – 6 months after the start of maintenance chemotherapy with olaparib – the patient is disease free. Conclusions: Second-line chemotherapy with a nonplatinum combination – trabectedin plus PLD – was effective in a BRCA2 mutation carrier with recurrent partially platinum-sensitive ovarian cancer.


Oncogene ◽  
2021 ◽  
Author(s):  
Zied Boudhraa ◽  
Kossay Zaoui ◽  
Hubert Fleury ◽  
Maxime Cahuzac ◽  
Sophie Gilbert ◽  
...  

AbstractWhile aneuploidy is a main enabling characteristic of cancers, it also creates specific vulnerabilities. Here we demonstrate that Ran inhibition targets epithelial ovarian cancer (EOC) survival through its characteristic aneuploidy. We show that induction of aneuploidy in rare diploid EOC cell lines or normal cells renders them highly dependent on Ran. We also establish an inverse correlation between Ran and the tumor suppressor NR1D1 and reveal the critical role of Ran/NR1D1 axis in aneuploidy-associated endogenous DNA damage repair. Mechanistically, we show that Ran, through the maturation of miR4472, destabilizes the mRNA of NR1D1 impacting several DNA repair pathways. We showed that NR1D1 interacts with both PARP1 and BRCA1 leading to the inhibition of DNA repair. Concordantly, loss of Ran was associated with NR1D1 induction, accumulation of DNA damages, and lethality of aneuploid EOC cells. Our findings suggest a synthetic lethal strategy targeting aneuploid cells based on their dependency to Ran.


2017 ◽  
Vol 22 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Katsutoshi Oda ◽  
Michihiro Tanikawa ◽  
Kenbun Sone ◽  
Mayuyo Mori-Uchino ◽  
Yutaka Osuga ◽  
...  

Surgery ◽  
2006 ◽  
Vol 139 (5) ◽  
pp. 704-706 ◽  
Author(s):  
Maryam Guiahi ◽  
Sheryl G.A. Gabram ◽  
Kathy S. Albain ◽  
Pauline Camacho ◽  
Bhuma Krishnamachari ◽  
...  

2009 ◽  
Vol 6 (10) ◽  
pp. 604-607 ◽  
Author(s):  
Seema Panchal ◽  
Orli Shachar ◽  
Frances O'Malley ◽  
Pavel Crystal ◽  
Jaime Escallon ◽  
...  

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