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KPT-330 has antitumour activity against non-small cell lung cancer.

  • Author(s): Sun, H;
  • Hattori, N;
  • Chien, W;
  • Sun, Q;
  • Sudo, M;
  • E-Ling, GL;
  • Ding, L;
  • Lim, SL;
  • Shacham, S;
  • Kauffman, M;
  • Nakamaki, T;
  • Koeffler, HP
  • et al.
Abstract

Background

We investigated the biologic and pharmacologic activities of a chromosome region maintenance 1 (CRM1) inhibitor against human non-small cell lung cancer (NSCLC) cells both in vitro and in vivo.

Methods

The in vitro and in vivo effects of a novel CRM1 inhibitor (KPT-330) for a large number of anticancer parameters were evaluated using a large panel of 11 NSCLC cell lines containing different key driver mutations. Mice bearing human NSCLC xenografts were treated with KPT-330, and tumour growth was assessed.

Results

KPT-330 inhibited proliferation and induced cell cycle arrest and apoptosis-related proteins in 11 NSCLC cells lines. Moreover, the combination of KPT-330 with cisplatin synergistically enhanced the cell kill of the NSCLC cells in vitro. Human NSCLC tumours growing in immunodeficient mice were markedly inhibited by KPT-330. Also, KPT-330 was effective even against NSCLC cells with a transforming mutation of either exon 20 of EGFR, TP53, phosphatase and tensin homologue, RAS or PIK3CA, suggesting the drug might be effective against a variety of lung cancers irrespective of their driver mutation.

Conclusions

Our results support clinical testing of KPT-330 as a novel therapeutic strategy for NSCLC.

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