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Nucleic acid targeting: towards personalized therapy for head and neck cancer

Oncogene volume 35, pages 3217–3226 (2016)Cite this article

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Abstract

In light of a detailed characterization of genetic aberrations in cancer, nucleic acid targeting represents an attractive therapeutic approach with significant translational potential. Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer deaths worldwide with stagnant 5-year survival rates. Advances in conventional treatment have done little to improve survival and combined chemoradiation is associated with significant adverse effects. Recent reports have characterized the genetic alterations in HNSCC and demonstrated that mutations confer resistance to conventional and molecular targeted therapies. The ability to use specific nucleic acid sequences to inhibit cancer-associated genes including non-druggable targets facilitates personalized medicine approaches with less adverse effects. Additionally, advances in drug delivery mechanisms have increased the transfection efficiency aiding in greater therapeutic responses. Given these advances, the stage has been set to translate the information garnered from genomic studies into personalized treatment strategies. Genes involved in the tumor protein 53 and epidermal growth factor receptor pathways have been extensively investigated and many promising preclinical studies have shown tumor inhibition through genetic modulation. We, and others, have demonstrated that targeting oncogene expression with gene therapy approaches is feasible in patients. Other methods such as RNA interference have proven to be effective and are potential candidates for clinical studies. This review summarizes the major advances in sequence-specific gene modulation in the preclinical setting and in clinical trials in head and neck cancer patients.

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Acknowledgements

We thank Dr Hinrich Staecker, Department of Otolaryngology, University of Kansas Medical Center, Kansas City, KS and Dr Stefan Rothenberg, K-State University, Manhattan, KS for critical review of the manuscript. We also thank Mr Phil Shafer for the artwork. We apologize to authors whose work was not cited due to space constraints. Department of Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center’s CCSG (1-P30-CA168524-02), and the Kansas Intellectual and Developmental Disabilities Center (NICHD HD00258) were the funding sources.

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Authors and Affiliations

  1. Department of Otolaryngology, University of Kansas Medical Center, Kansas City, KS, USA

    S M Parsel & S M Thomas

  2. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA

    J R Grandis

  3. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, USA

    S M Thomas

  4. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA

    S M Thomas

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  1. S M Parsel
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Correspondence to S M Thomas.

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Parsel, S., Grandis, J. & Thomas, S. Nucleic acid targeting: towards personalized therapy for head and neck cancer. Oncogene 35, 3217–3226 (2016). https://doi.org/10.1038/onc.2015.424

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