دورية أكاديمية
The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models
| العنوان: | The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models |
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| المؤلفون: | Ho, GY, Vandenberg, CJ, Lim, R, Christie, EL, Garsed, DW, Lieschke, E, Nesic, K, Kondrashova, O, Ratnayake, G, Radke, M, Penington, JS, Carmagnac, A, Heong, V, Kyran, EL, Zhang, F, Traficante, N, Huang, R, Dobrovic, A, Swisher, EM, McNally, O, Kee, D, Wakefield, MJ, Papenfuss, AT, Bowtell, DDL, Barker, HE, Scott, CL |
| بيانات النشر: | SAGE PUBLICATIONS LTD |
| سنة النشر: | 2023 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | BACKGROUND: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have de novo platinum-refractory disease. OBJECTIVES: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC. DESIGN AND METHODS: Of 13 PRR HGSC PDX, six were primary PRR, derived from chemotherapy-naïve samples (one was BRCA2 mutant) and seven were from samples obtained following chemotherapy treatment in the clinic (five were mutant for either BRCA1 or BRCA2 (BRCA1/2), four with prior PARPi exposure), recapitulating the population of individuals with aggressive treatment-resistant HGSC in the clinic. Molecular analyses and in vivo treatment studies were undertaken. RESULTS: Seven out of thirteen PRR PDX (54%) were sensitive to treatment with the AMA, eribulin (time to progressive disease (PD) ⩾100 days from the start of treatment) and 11 out of 13 PDX (85%) derived significant benefit from eribulin [time to harvest (TTH) for each PDX with p < 0.002]. In 5 out of 10 platinum-refractory HGSC PDX (50%) and one out of three platinum-resistant PDX (33%), eribulin was more efficacious than was cisplatin, with longer time to PD and significantly extended TTH (each PDX p < 0.02). Furthermore, four of these models were extremely sensitive to all three AMA tested, maintaining response until the end of the experiment (120d post-treatment start). Despite harbouring secondary BRCA2 mutations, two BRCA2-mutant PDX models derived from heavily pre-treated individuals were sensitive to AMA. PRR HGSC PDX models showing greater sensitivity to AMA had high proliferative indices and oncogene expression. Two PDX models, both with prior chemotherapy and/or PARPi exposure, were refractory to all AMA, one of which harboured the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1758-8340 1758-8359 |
| العلاقة: | NHMRC/400281; NHMRC/400413; NHMRC/1081178; pii: 10.1177_17588359231208674; Ho, G. Y., Vandenberg, C. J., Lim, R., Christie, E. L., Garsed, D. W., Lieschke, E., Nesic, K., Kondrashova, O., Ratnayake, G., Radke, M., Penington, J. S., Carmagnac, A., Heong, V., Kyran, E. L., Zhang, F., Traficante, N., Huang, R., Dobrovic, A., Swisher, E. M. ,. Scott, C. L. (2023). The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models. THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, 15, https://doi.org/10.1177/17588359231208674Test.; http://hdl.handle.net/11343/344499Test |
| الإتاحة: | https://doi.org/10.1177/17588359231208674Test http://hdl.handle.net/11343/344499Test |
| حقوق: | CC BY-NC ; https://creativecommons.org/licenses/by-nc/4.0Test |
| رقم الانضمام: | edsbas.70C94E4A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17588340 17588359 |
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