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A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer

Oncogene volume 34, pages 3547–3555 (2015)Cite this article

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Abstract

Targeted cancer therapies, although often effective, have limited utility owing to preexisting primary or acquired secondary resistance. Consequently, agents are sometimes used in combination to simultaneously affect multiple targets. MicroRNA mimics are excellent therapeutic candidates because of their ability to repress multiple oncogenic pathways at once. Here we treated the aggressive Kras;p53 non-small cell lung cancer mouse model and demonstrated efficacy with a combination of two tumor-suppressive microRNAs (miRNAs). Systemic nanodelivery of miR-34 and let-7 suppressed tumor growth leading to survival advantage. This combinatorial miRNA therapeutic approach engages numerous components of tumor cell-addictive pathways and highlights the ability to deliver multiple miRNAs in a safe and effective manner to target lung tissue.

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Acknowledgements

ALK was supported by an American Cancer Society Fellowship (PF-11-244-01) and an NIH Pathway to Independence Award (CA178091). This work was supported by a grant to FJS from the NIH (CA131301) and by a commercialization grant from the Cancer Prevention Research Institute of Texas (CPRIT) to AGB.

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Authors and Affiliations

  1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    A L Kasinski, C Stahlhut, E Shimer, X Chen & F J Slack

  2. Department of Biological Sciences, Purdue University, West Lafayette, IN, USA

    A L Kasinski & E Orellana

  3. Mirna Therapeutics, Inc., Austin, TX, USA

    K Kelnar, J Zhao, S Dysart & A G Bader

  4. Department of Pathology, Harvard Medical School, Boston, MA, USA

    F J Slack

Authors
  1. A L Kasinski
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  2. K Kelnar
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  3. C Stahlhut
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  4. E Orellana
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  5. J Zhao
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  6. E Shimer
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  7. S Dysart
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  8. X Chen
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  9. A G Bader
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  10. F J Slack
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Corresponding authors

Correspondence to A G Bader or F J Slack.

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Competing interests

KK, JZ and AGB are employees of Mirna Therapeutics, which develops miRNA-based therapies. SD is a former employee of Mirna Therapeutics. FJS is a consultant for Mirna Therapeutics. KK, JZ, AGB and FJS are shareholders of Mirna Therapeutics. The remaining authors declare no conflict of interest.

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Kasinski, A., Kelnar, K., Stahlhut, C. et al. A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer. Oncogene 34, 3547–3555 (2015). https://doi.org/10.1038/onc.2014.282

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  • DOI: https://doi.org/10.1038/onc.2014.282

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