The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models

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...

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Veröffentlicht in:Therapeutic advances in medical oncology 2023-01, Vol.15, p.17588359231208674-17588359231208674
Hauptverfasser: Ho, Gwo Yaw, Vandenberg, Cassandra J., Lim, Ratana, Christie, Elizabeth L., Garsed, Dale W., Lieschke, Elizabeth, Nesic, Ksenija, Kondrashova, Olga, Ratnayake, Gayanie, Radke, Marc, Penington, Jocelyn S., Carmagnac, Amandine, Heong, Valerie, Kyran, Elizabeth L., Zhang, Fan, Traficante, Nadia, Huang, Ruby, Dobrovic, Alexander, Swisher, Elizabeth M., McNally, Orla, Kee, Damien, Wakefield, Matthew J., Papenfuss, Anthony T., Bowtell, David D. L., Barker, Holly E., Scott, Clare L.
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Sprache:eng
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Zusammenfassung: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 
ISSN:1758-8359
1758-8340
1758-8359
DOI:10.1177/17588359231208674