EGFR inhibition in non-small cell lung cancer: Current evidence and future directions

被引:25
作者
Chi A. [1 ]
Remick S. [2 ]
Tse W. [3 ]
机构
[1] Department of Radiation Oncology, West Virginia University, Morgantown, WV
[2] Mary-Babb Randolph Cancer Center, West Virginia University, Morgantown, WV
[3] Department of Hematology and Oncology, West Virginia University, Morgantown, WV
关键词
EGFR; EGFR mutations; NSCLC; Radiotherapy; Resistance;
D O I
10.1186/2050-7771-1-2
中图分类号
学科分类号
摘要
EGFR inhibition has emerged to be an important strategy in the treatment of non-small cell lung cancer (NSCLC). Small molecule tyrosine kinase inhibitors (TKIs) and mono-clonal antibodies (mAbs) to the EGFR have been tested in multiple large randomized phase III studies alone or combined with chemotherapy, as well as small phase I-II studies which investigated their efficacy as radiosensitizers when combined with radiotherapy. In this review, we described the current clinical outcome after treatment with EGFR TKIs and mAbs alone or combined with chemotherapy in advanced stage NSCLC, as well as the early findings in feasibility/phase I or II studies regarding to whether EGFR TKI or mAb can be safely and effectively combined with radiotherapy in the treatment of locally advanced NSCLC. Furthermore, we explore the potential predictive biomarkers for response to EGFR TKIs or mAbs in NSCLC patients based on the findings in the current clinical trials; the mechanisms of resistance to EGFR inhibition; and the strategies of augmenting the antitumor activity of the EGFR inhibitors alone or when combined with chemotherapy or radiotherapy. © 2013 Chi et al.; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 86 条
[1]  
Mendelsohn J., Baselga J., Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer, J Clin Oncol, 21, pp. 2787-2799, (2003)
[2]  
Yoshida T., Zhang G., Haura E.B., Targeting epidermal growth factor receptor: Central signaling kinase in lung cancer, Biochem Pharmacol, 80, pp. 613-623, (2010)
[3]  
Ono M., Kuwano M., Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs, Clin Cancer Res, 12, pp. 7242-7251, (2006)
[4]  
Cohen S., Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal, J Biol Chem, 237, pp. 1555-1562, (1962)
[5]  
Ausborn N.L., Le Q.T., Bradley J.D., Et al., Molecular profiling to optimize treatment in non-small cell lung cancer: a review of potential molecular targets for radiation therapy by the translational research program of the Radiation Therapy Oncology Group, Int J Radiat Oncol Biol Phys, 83, (2012)
[6]  
Mendelsohn J., Baselga J., The EGF receptor family as targets for cancer therapy, Oncogene, 19, pp. 6550-6565, (2000)
[7]  
Harari P.M., Huang S.M., Combining EGFR inhibitors with radiation or chemotherapy: will preclinical studies predict clinical results?, Int J Radiat Oncol Biol Phys, 58, pp. 976-983, (2004)
[8]  
Milas L., Fan Z., Andratschke N.H., Ang K.K., Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies, Int J Radiat Oncol Biol Phys, 58, pp. 966-971, (2004)
[9]  
Raben D., Helfrich B., Bunn P.A., Targeted therapies for non-small-cell lung cancer: Biology, rationale, and preclinical results from a radiation oncology perspective, Int J Radiat Oncol Biol Phys, 59, (2004)
[10]  
Cappuzzo F., Hirsch F.R., Rossi E., Et al., Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small cell lung cancer, J Natl Cancer Inst, 97, pp. 643-655, (2005)