New strategies in ovarian cancer treatment

Lee, Jung‐Min; Minasian, Lori M.; Kohn, Elise C.

doi:10.1002/cncr.32544

Cited by 96 publications

(70 citation statements)

References 38 publications

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“…The complexity of DNA repair/DDR, as nicely illustrated by Brown et al 2017 [185], offers the use of other inhibitors as well. For instance, inhibitors of CHK1 and CHK2 appeared as promising therapeutics for OvC, both as monotherapy or in combination with PARPi [186,187]. The other example is based on the interaction of ATM inhibition in combination with APE1 inhibitors (APE1i) or XRCC1 loss of function [188,189].…”

Section: Interplay Of Dna Repair Pathwaysmentioning

confidence: 99%

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Tomášová

Čumová

Šeborová

et al. 2020

Cancers

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There is ample evidence for the essential involvement of DNA repair and DNA damage response in the onset of solid malignancies, including ovarian cancer. Indeed, high-penetrance germline mutations in DNA repair genes are important players in familial cancers: BRCA1, BRCA2 mutations or mismatch repair, and polymerase deficiency in colorectal, breast, and ovarian cancers. Recently, some molecular hallmarks (e.g., TP53, KRAS, BRAF, RAD51C/D or PTEN mutations) of ovarian carcinomas were identified. The manuscript overviews the role of DNA repair machinery in ovarian cancer, its risk, prognosis, and therapy outcome. We have attempted to expose molecular hallmarks of ovarian cancer with a focus on DNA repair system and scrutinized genetic, epigenetic, functional, and protein alterations in individual DNA repair pathways (homologous recombination, non-homologous end-joining, DNA mismatch repair, base- and nucleotide-excision repair, and direct repair). We suggest that lack of knowledge particularly in non-homologous end joining repair pathway and the interplay between DNA repair pathways needs to be confronted. The most important genes of the DNA repair system are emphasized and their targeting in ovarian cancer will deserve further attention. The function of those genes, as well as the functional status of the entire DNA repair pathways, should be investigated in detail in the near future.

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Section: Interplay Of Dna Repair Pathwaysmentioning

confidence: 99%

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Tomášová

Čumová

Šeborová

et al. 2020

Cancers

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“…Based on the relative worse prognosis of advanced-stage ETOC and PPSC, many new modalities and strategies have been recently developed [56][57][58][59]. Although some of them have been already recommended by updated NCCN guidelines for ETOC and PPSC treatment [4,26], they are not widely used in the routine clinical practice [60].…”

Section: Current Standard Of Treatmentmentioning

confidence: 99%

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

Huang

Chen

Lee

et al. 2020

IJERPH

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The use of weekly chemotherapy for the treatment of patients with advanced-stage serous-type epithelial Tubo-ovarian cancer (ETOC), and primary peritoneal serous carcinoma (PPSC) is acceptable as the front-line postoperative chemotherapy after primary cytoreductive surgery (PCS). The main component of dose-dense chemotherapy is weekly paclitaxel (80 mg/m2), but it would be interesting to know what is the difference between combination of triweekly cisplatin (20 mg/m2) or triweekly carboplatin (carboplatin area under the curve 5-7 mg/mL per min [AUC 5-7]) in the dose-dense paclitaxel regimen. Therefore, we compared the outcomes of women with Gynecology and Obstetrics (FIGO) stage IIIC ETOC and PPSC treated with PCS and a subsequent combination of dose-dense weekly paclitaxel and triweekly cisplatin (paclitaxel–cisplatin) or triweekly carboplatin using AUC 5 (paclitaxel–carboplatin). Between January 2010 and December 2016, 40 women with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC EOC, FTC, or PPSC were enrolled, including 18 treated with paclitaxel–cisplatin and the remaining 22 treated with paclitaxel–carboplatin. There were no statistically significant differences in disease characteristics of patients between two groups. Outcomes in paclitaxel–cisplatin group seemed to be little better than those in paclitaxel–carboplatin (median progression-free survival [PFS] 30 versus 25 months as well as median overall survival [OS] 58.5 versus 55.0 months); however, neither reached a statistically significant difference. In terms of adverse events (AEs), patients in paclitaxel–carboplatin group had more AEs, with a higher risk of neutropenia and grade 3/4 neutropenia, and the need for a longer period to complete the front-line chemotherapy, and the latter was associated with worse outcome for patients. We found that a period between the first-time chemotherapy to the last dose (6 cycles) of chemotherapy >21 weeks was associated with a worse prognosis in patients compared to that ≤21 weeks, with hazard ratio (HR) of 81.24 for PFS and 9.57 for OS. As predicted, suboptimal debulking surgery (>1 cm) also contributed to a worse outcome than optimal debulking surgery (≤1 cm) with HR of 14.38 for PFS and 11.83 for OS. Based on the aforementioned findings, both regimens were feasible and effective, but maximal efforts should be made to achieve optimal debulking surgery and following the on-schedule administration of dose-dense weekly paclitaxel plus triweekly platinum compounds. Randomized trials validating the findings are warranted.

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“…Standard therapy for EOC is of the combined surgical debulking and platinum-based chemotherapy, but less than half respond [4].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of microRNA-125b and its contribution to ovarian carcinogenesis

Guan

Wang

et al. 2020

Bioengineered

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The underlying mechanisms of recurrence and metastasis of epithelial ovarian cancer (EOC) are largely unknown. In the present study, we investigated the clinical significance of microRNA-125b (miR-125b) and its role in ovarian tumorigenesis and progression. Seventy patients of EOC and paired tissues were enrolled from 2015 to 2017. qRT-PCR was used to evaluate miR-125b expression in tumor tissues and EOC cell line. Gain-and-loss function of miR-125b was achieved to explore the changes in cell biological function. We found that miR-125b expression in EOC tissues, especially in the high-grade tissues (P < 0.001), was significantly lower compared to the matched adjacent noncancerous tissues and associated with pathological type, stage, and overall survival (P < 0.05). Upregulation of miR-125b promoted apoptosis and decreased cell survival rate and migration, and vice versa in vitro. Mechanistically, miR-125b negatively regulated S100A4, a metastasis-associated protein. MiR-125b overexpression significantly decreased tumor growth and inhibited lung metastasis in vivo. Our results supported that miR-125b contributes to the progression of EOC by targeting S100A4. It potentially acts as a potential biomarker and therapeutic target of EOC.

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New strategies in ovarian cancer treatment

Cited by 96 publications

References 38 publications

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

Clinical significance of microRNA-125b and its contribution to ovarian carcinogenesis

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