Cancer Research and Treatment

Original Articles

Gynecologic Cancer

Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells: Hye-yon Cho, Yong-Beom Kim, Wook-ha Park, Jae Hong No; Cancer Res Treat. 2021;53(3):819-828. Published online December 16, 2020; DOI: https://doi.org/10.4143/crt.2020.1013

Purpose
This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair.
Materials and Methods
We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3).
Results
We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination–mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib.
Conclusion
Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Citations

Citations to this article as recorded by

ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors
Hannah L. Smith, Elaine Willmore, Lisa Prendergast, Nicola J. Curtin
British Journal of Cancer.2024; 131(5): 905. CrossRef
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Update on Combination Strategies of PARP Inhibitors
Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
Cancer Control.2024;[Epub] CrossRef
Molecular Methods for Increasing the Effectiveness of Ovarian Cancer Treatment: A Systematic Review
Zuzanna Chilimoniuk, Agata Rocka, Martyna Stefaniak, Żaklina Tomczyk, Faustyna Jasielska, Dominika Madras, Agata Filip
Future Oncology.2022; 18(13): 1627. CrossRef
A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer
Panagiotis A. Konstantinopoulos, Jung-min Lee, Bo Gao, Rowan Miller, Jung-Yun Lee, Nicoletta Colombo, Ignace Vergote, Kelly M. Credille, Suzanne R. Young, Samuel McNeely, Xuejing Aimee Wang, Aimee Bence Lin, Ronnie Shapira-Frommer
Gynecologic Oncology.2022; 167(2): 213. CrossRef
Pharmacological Poly (ADP-Ribose) Polymerase Inhibitors Decrease Mycobacterium tuberculosis Survival in Human Macrophages
Cassandra L. R. van Doorn, Sanne A. M. Steenbergen, Kimberley V. Walburg, Tom H. M. Ottenhoff
Frontiers in Immunology.2021;[Epub] CrossRef

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Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: Maria Lee, Yumi Lee, Kidong Kim, Eun Young Park, Myong Cheol Lim, Jung-Sup Kim, Hee Seung Kim, Yong-Beom Kim, Yong-Man Kim, Jungnam Joo, Sang Yoon Park, Chel Hun Choi, Jae-Hoon Kim; Cancer Res Treat. 2019;51(1):112-118. Published online March 7, 2018; DOI: https://doi.org/10.4143/crt.2017.361

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility.
Materials and Methods
In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated.
Results
Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting.
Conclusion
Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

Citations

Citations to this article as recorded by

Peripheral Neuropathy Instruments for Individuals with Cancer: A COSMIN-Based Systematic Review of Measurement Properties
Silvia Belloni, Arianna Magon, Chiara Giacon, Francesca Savioni, Gianluca Conte, Rosario Caruso, Cristina Arrigoni
Current Oncology.2024; 31(12): 7828. CrossRef
Assessing the quality of patient-reported outcome measurements for gynecological cancers: a systematic review
Charlotte L Moss, Teresa Guerrero-Urbano, Ingrid White, Benjamin Taylor, Rebecca Kristeleit, Ana Montes, Louis Fox, Katharina Beyer, Monika Sztankay, Maria M Ratti, Elena S Sisca, Alexandra Derevianko, Steven MacLennan, Nicholas Wood, Lisa M Wintner, Miek
Future Oncology.2023; 19(9): 663. CrossRef
Validity and Reliability of the Turkish Version of National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18) and Neurotoxicity-4 (NTX-4) for Patients with Advanced Ovarian Cancer
Husnu Tore Yavuzsen, Sukriye Cansu Gulteki̇n, Karya Polat, Murat Keser, Zeynep Gulsum Guc, Merve Keskinkilic, Tugba Yavuzsen, Didem Karadibak, Sourav Panja
European Journal of Cancer Care.2023; 2023: 1. CrossRef
Assessing chemotherapy-induced peripheral neuropathy with patient reported outcome measures: a systematic review of measurement properties and considerations for future use
Tiffany Li, Susanna B. Park, Eva Battaglini, Madeleine T. King, Matthew C. Kiernan, David Goldstein, Claudia Rutherford
Quality of Life Research.2022; 31(11): 3091. CrossRef
Influence of chemotherapy on postural control and quality of life in women with gynaecological cancer: a protocol of a prospective observational study
Aline Reinmann, Anne-Violette Bruyneel, Joseph Gligorov, Serge Mesure, Christophe Combescure, Thibaud Koessler, Alexandre Bodmer
BMJ Open.2022; 12(9): e061664. CrossRef

8,261 View
185 Download
5 Web of Science
5 Crossref

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