Title |
Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer
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Published in |
Breast Cancer Research, August 2017
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DOI | 10.1186/s13058-017-0878-6 |
Pubmed ID | |
Authors |
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W. Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T. Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam |
Abstract |
Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy. In vivo efficacy was tested both as a single agent and in combination therapy in TNBC patient-derived xenografts (PDXs). Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively). Collectively, these findings strongly suggest that selinexor is a promising therapeutic agent for TNBC as a single agent and in combination with standard chemotherapy. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 49 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 12% |
Student > Postgraduate | 5 | 10% |
Student > Bachelor | 5 | 10% |
Other | 4 | 8% |
Researcher | 3 | 6% |
Other | 8 | 16% |
Unknown | 18 | 37% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 16 | 33% |
Medicine and Dentistry | 10 | 20% |
Agricultural and Biological Sciences | 3 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Engineering | 1 | 2% |
Other | 0 | 0% |
Unknown | 17 | 35% |