Gene Therapy for Radiation-Induced Salivary Hypofunction

  • Bruce J. BaumEmail author


  • Often patients who have radiation-induced salivary hypofunction are told by their surgeons or oncologists that they should be happy “they are cured” and not complain about a “minor side effect,” i.e., a small problem such as having too little saliva due to their cancer treatment. Even patients for whom gene or pharmacological therapy are not options benefit greatly from a clinician’s attention and careful instructions on how to care for their oral health and how to chew and swallow deliberately.

  • It must be recognized that gene therapy is still in its developmental stages. The vectors used now to transfer genes into salivary glands and other tissues doubtless will be viewed as primitive in one to two decades.

  • Indeed, it may be feasible within a decade or so to prevent radiation damage to healthy salivary glands using gene transfer technology alone or in conjunction with improved advanced radiotherapy techniques and/or pharmacological agents.



I am extremely grateful to the Intramural Research Program of the National Institute of Dental and Craniofacial Research for supporting my research and enabling everything that is mentioned in this chapter. I am also extremely grateful to my many wonderful colleagues at NIH and elsewhere who worked so hard to make a 1991 vision into a clinical reality.


  1. 1.
    Fox PC, van der Ven PF, Sonies BC, et al. Xerostomia: evaluation of a symptom with increasing significance. J Am Dent Assoc. 1985;110:519–25.CrossRefPubMedGoogle Scholar
  2. 2.
    Ship JA, Fox PC, Baum BJ. How much saliva is enough? Normal function defined. J Am Dent Assoc. 1991;122:63–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Heft MW, Bruce BJ. Unstimulated and stimulated parotid salivary flow rate in individuals of different ages. J Dent Res. 63:1182–5.Google Scholar
  4. 4.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.CrossRefPubMedGoogle Scholar
  5. 5.
    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Baum BJ, Zheng C, Alevizos I, et al. Development of a gene transfer-based treatment for radiation-induced salivary hypofunction. Oral Oncol. 2010;46:4–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Vissink A, Mitchell JB, Baum BJ, et al. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers. Int J Radiat Oncol Biol Phys. 2010;78:983–91.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Samuni Y, Baum BJ. Gene delivery in salivary glands: from the bench to the clinic. Biochim Biophys Acta. 1812;2011:1515–21.Google Scholar
  9. 9.
    Strietzel FP, Lafaurie GI, Mendoza GR, et al. Efficacy and safety of an intraoral electrostimulation device for xerostomia relief: a multicenter randomized trial. Arthritis Rheum. 2011;63:180–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Baum BJ, Alevizos A, Zheng C, et al. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci U S A. 2012;109:19403–7.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gao R, Yan X, Zheng C, et al. AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands. Gene Ther. 2011;18:38–42.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang Z, Zourelias L, Wu C, et al. Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion. Gene Ther. 2015;22:739–49.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Timiri Shanmugam PS, Dayton RD, Palaniyandi S, et al. Recombinant AAV9-TLK1B administration ameliorates fractionated radiation-induced xerostomia. Hum Gene Ther. 2013;24:604–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Arany S, Benoit DS, Dewhurst S, Ovitt CE. Nanoparticle-mediated gene silencing confers radioprotection to salivary glands in vivo. Mol Ther. 2013;21:1182–94.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Pai S, Ghezzi ES, Ship JA. Development of a visual analogue scale questionnaire for subjective assessment of salivary dysfunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:311–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Chi-Fishman G, Sonies BC. Effects of systematic bolus viscosity and volume changes on hyoid movement kinematics. Dysphagia. 2001;17:278–87.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.National Institutes of Health Scientist Emeritus, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human ServicesBethesdaUSA

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