The predictive and therapeutic value of thymidine phosphorylase and dihydropyrimidine dehydrogenase in capecitabine (Xeloda)-based chemotherapy for head and neck cancer

Koichiro Saito, Khurram Khan, Shu Zhen Yu, Steve Ronson, Joung Rhee, Gouyan Li, David Van Echo, Mohan Suntharalingam, Bert W. O'Malley, Daqing Li

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives: To evaluate whether two molecular biomarkers, thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), could be clinically useful in predicting and improving the chemotherapeutic outcome of the oral fluoropyrimidine capecitabine (5'-DFUR or Xeloda ®), in the treatment of human head and neck squamous cell carcinoma (HNSCC). Experimental Design: Quantitative reversetranscriptase polymerase chain reaction was used to determine the TP and DPD expression levels in different HNSCC cell lines. The TP to DPD ratio was calculated and compared to the relative chemosensitivity between cell lines after treatment with 5'-DFUR. The effect of TP transgene expression to alter the TP to DPD ratio and hence optimize the therapeutic outcome of capecitabine treatment was further evaluated in a murine model of human HNSCC using immunohistochemistry to detect TP and DPD expression in vivo. Results: No correlation was detected between sensitivity to 5'-DFUR and the relative expression levels of TP or DPD in the multiple HNSCC cell lines tested. However, significant correlation was observed between the TP to DPD ratio versus drug resistance of the HNSCC cells (r=-0.914, ρ=0.0281). In addition, we demonstrate that transgene expression of TP significantly enhanced the tumoricidal effect of capecitabine in HNSCC tumors with otherwise low endogenous TP to DPD ratios. This antitumor effect was observed up to 30 days after treatment. Conclusions: The results of this study suggest that HNSCC patients who would most benefit from capecitabine-based chemotherapy could be identified by examining the TP to DPD ratio of their tumors. Furthermore, we demonstrate the potential role of TP gene therapy in TP to DPD ratio manipulation to optimize the tumoricidal effect of capecitabine.

Original languageEnglish
Pages (from-to)82-88
Number of pages7
JournalLaryngoscope
Volume119
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Keywords

  • Capecitabine
  • Dihydropyrimidine dehydrogenase
  • HNSCC
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Otorhinolaryngology

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    Saito, K., Khan, K., Yu, S. Z., Ronson, S., Rhee, J., Li, G., Van Echo, D., Suntharalingam, M., O'Malley, B. W., & Li, D. (2009). The predictive and therapeutic value of thymidine phosphorylase and dihydropyrimidine dehydrogenase in capecitabine (Xeloda)-based chemotherapy for head and neck cancer. Laryngoscope, 119(1), 82-88. https://doi.org/10.1002/lary.20003