Targeting Apoptosis to Overcome Cisplatin Resistance: A Translational Study in Head and Neck Cancer

Joshua A. Bauer, Bhavna Kumar, Kitrina G. Cordell, Mark E. Prince, Huong H. Tran, Gregory T. Wolf, Douglas B. Chepeha, Theodoros N. Teknos, Steven Wang, Avraham Eisbruch, Christina I. Tsien, Susan G. Urba, Francis P. Worden, Julia Lee, Kent A. Griffith, Jeremy M.G. Taylor, Nisha D'Silva, Shaomeng J. Wang, Keith G. Wolter, Bradley HensonSusan G. Fisher, Thomas E. Carey, Carol R. Bradford

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose: Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed. Methods and Materials: Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL. Results: HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bcl-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wild-type p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC. Conclusion: Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53.

Original languageEnglish
Pages (from-to)S106-S108
JournalInternational Journal of Radiation Oncology Biology Physics
Volume69
Issue number2 SUPPL.
DOIs
StatePublished - Oct 1 2007

Keywords

  • Chemoradiation
  • Head and neck cancer
  • Larynx preservation
  • Predictive markers

Fingerprint Dive into the research topics of 'Targeting Apoptosis to Overcome Cisplatin Resistance: A Translational Study in Head and Neck Cancer'. Together they form a unique fingerprint.

  • Cite this

    Bauer, J. A., Kumar, B., Cordell, K. G., Prince, M. E., Tran, H. H., Wolf, G. T., Chepeha, D. B., Teknos, T. N., Wang, S., Eisbruch, A., Tsien, C. I., Urba, S. G., Worden, F. P., Lee, J., Griffith, K. A., Taylor, J. M. G., D'Silva, N., Wang, S. J., Wolter, K. G., ... Bradford, C. R. (2007). Targeting Apoptosis to Overcome Cisplatin Resistance: A Translational Study in Head and Neck Cancer. International Journal of Radiation Oncology Biology Physics, 69(2 SUPPL.), S106-S108. https://doi.org/10.1016/j.ijrobp.2007.05.080