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 Henson; Susan G. Fisher; Thomas E. Carey; Carol R. Bradford

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
, 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

Research output: Contribution to journal › Article › peer-review

32 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 language	English (US)
Pages (from-to)	S106-S108
Journal	International Journal of Radiation Oncology Biology Physics
Volume	69
Issue number	2 SUPPL.
DOIs	https://doi.org/10.1016/j.ijrobp.2007.05.080
State	Published - Oct 1 2007
Externally published	Yes

Keywords

Chemoradiation
Head and neck cancer
Larynx preservation
Predictive markers

ASJC Scopus subject areas

Radiation
Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/j.ijrobp.2007.05.080

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

Bauer, JA, Kumar, B, Cordell, KG, Prince, ME, Tran, HH, Wolf, GT, Chepeha, DB, Teknos, TN, Wang, S, Eisbruch, A, Tsien, CI, Urba, SG, Worden, FP, Lee, J, Griffith, KA, Taylor, JMG, D'Silva, N, Wang, SJ, Wolter, KG, Henson, B, Fisher, SG, Carey, TE & Bradford, CR 2007, 'Targeting Apoptosis to Overcome Cisplatin Resistance: A Translational Study in Head and Neck Cancer', International Journal of Radiation Oncology Biology Physics, vol. 69, no. 2 SUPPL., pp. S106-S108. https://doi.org/10.1016/j.ijrobp.2007.05.080

@article{f298919b14a746c790b2ae06b68bbfd7,

title = "Targeting Apoptosis to Overcome Cisplatin Resistance: A Translational Study in Head and Neck Cancer",

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.",

keywords = "Chemoradiation, Head and neck cancer, Larynx preservation, Predictive markers",

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

note = "Funding Information: Supported by the National Institutes of Health National Institute of Dental and Craniofacial Research (R01 DE13346), National Institute of Deafness and Other Communication Disorders (P30 DC 05188), and National Cancer Institute (R01 CA83087), a University of Michigan's Head and Neck Cancer SPORE grant (P50 CA97248), and a Cancer Center Support grant (P30 CA46592). ",

year = "2007",

month = oct,

day = "1",

doi = "10.1016/j.ijrobp.2007.05.080",

language = "English (US)",

volume = "69",

pages = "S106--S108",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier Inc.",

number = "2 SUPPL.",

}

TY - JOUR

T1 - Targeting Apoptosis to Overcome Cisplatin Resistance

T2 - A Translational Study in Head and Neck Cancer

AU - Bauer, Joshua A.

AU - Kumar, Bhavna

AU - Cordell, Kitrina G.

AU - Prince, Mark E.

AU - Tran, Huong H.

AU - Wolf, Gregory T.

AU - Chepeha, Douglas B.

AU - Teknos, Theodoros N.

AU - Wang, Steven

AU - Eisbruch, Avraham

AU - Tsien, Christina I.

AU - Urba, Susan G.

AU - Worden, Francis P.

AU - Lee, Julia

AU - Griffith, Kent A.

AU - Taylor, Jeremy M.G.

AU - D'Silva, Nisha

AU - Wang, Shaomeng J.

AU - Wolter, Keith G.

AU - Henson, Bradley

AU - Fisher, Susan G.

AU - Carey, Thomas E.

AU - Bradford, Carol R.

N1 - Funding Information: Supported by the National Institutes of Health National Institute of Dental and Craniofacial Research (R01 DE13346), National Institute of Deafness and Other Communication Disorders (P30 DC 05188), and National Cancer Institute (R01 CA83087), a University of Michigan's Head and Neck Cancer SPORE grant (P50 CA97248), and a Cancer Center Support grant (P30 CA46592).

PY - 2007/10/1

Y1 - 2007/10/1

N2 - 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.

AB - 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.

KW - Chemoradiation

KW - Head and neck cancer

KW - Larynx preservation

KW - Predictive markers

UR - https://www.scopus.com/pages/publications/34548456063

UR - https://www.scopus.com/pages/publications/34548456063#tab=citedBy

U2 - 10.1016/j.ijrobp.2007.05.080

DO - 10.1016/j.ijrobp.2007.05.080

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C2 - 17848273

AN - SCOPUS:34548456063

SN - 0360-3016

VL - 69

SP - S106-S108

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 2 SUPPL.

ER -

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

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