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Tumor Biology

, Volume 36, Issue 4, pp 2993–2999 | Cite as

Acquired resistance to EGFR tyrosine kinase inhibitor in A431 squamous cell carcinoma xenografts is mediated by c-Kit pathway transduction

  • Lixia Zhang
  • Xiaokun Yang
  • Bei Zhao
  • Zhen Cai
Research Article

Abstract

Epidermal growth factor inhibitors (EGFRIs), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, all responding patients eventually developed acquired resistance to EGFRIs and the mechanisms of acquired resistance invariably develops. In the current study, we reported the tumor xenografts of the human A431 squamous cell carcinoma, after 25-week consecutive therapy with EGFR inhibitor (gefitinib) that developed resistance as a result of c-Kit overexpression. Moreover, combined therapeutic inhibition of EGFR and c-Kit may abrogate this acquired mechanism of drug resistance due to an enhanced apoptotic effect in gefitinib-resistant xenograft model. Taken together, the results suggest that at least in the A431 xenograft model displaying acquired resistance to gefitinib can emerge in vivo, at least in part, by mechanisms involving the c-Kit overexpression.

Keywords

EGFR A431 c-Kit Squamous cell carcinoma 

Notes

Acknowledgments

The authors thank Shang Wu for bioinformatics analysis of the Gene Chip of SNP 6.0 and U133 plus 2.0 arrays’ data.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Dermatology and VenereologySichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina
  2. 2.Department of EmergencyChengdu Military General HospitalChengduChina
  3. 3.Department of Plastic SurgerySichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina

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