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. 2007;69(2 Suppl):S106-8.
doi: 10.1016/j.ijrobp.2007.05.080.

Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer

Joshua A Bauer  1 , 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 Henson, Susan G Fisher, Thomas E Carey, Carol R Bradford
Affiliations

Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer

Joshua A Bauer et al. Int J Radiat Oncol Biol Phys. 2007.

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.

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Conflict of interest statement

Conflict of interest statement: No conflict of interest

Figures

Figure 1
Figure 1
Treatment selection based upon response to induction chemotherapy improves survival rates in advanced larynx cancer (A). Improved survival of patients selected for concomitant chemoradiation based upon favorable response to induction chemotherapy (UMCC 9520) vs. historical control (VA268). (B). Patients whose tumors expressed the lowest proportion of Bcl-xL in UMCC 9520 had 100% disease free survival.
See this image and copyright information in PMC

References

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