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- Title
Upregulation of Bcl2 in NSCLC with acquired resistance to EGFR-TKI.
- Authors
Cheong, Hio Teng; Xu, Fei; Choy, Chi Tung; Hui, Connie Wun Chun; Mok, Tony Shu Kam; Wong, Chi Hang
- Abstract
Lung cancer has the highest incidence and mortality rate worldwide among all malignancy-associated mortalities, of which non-small cell lung cancer accounts for 80% of all cases. Resistance against epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) develops following 8-12 months of disease progression, and is a critical issue. HCC827 cell lines with resistance to EGFR-TKIs were successfully screened. The half maximal inhibitory concentration values were 1,000-fold higher than the values for the parental HCC827 cell line, thereby demonstrating cross-resistance against the same family of TKIs. The expression of B-cell lymphoma 2 (Bcl2) was markedly increased in the resistant clones, as well as in the patient biopsies. The phosphatase and tensin homolog phosphoinositide 3-kinase signaling axis is a potential mechanism for acquiring resistance, and therefore targeting Bcl2 may be a useful strategy for further investigations.
- Subjects
NON-small-cell lung carcinoma; EPIDERMAL growth factor receptors regulation; PROTEIN-tyrosine kinase inhibitors; BCL-2 proteins; CANCER chemotherapy; PATIENTS
- Publication
Oncology Letters, 2018, Vol 15, Issue 1, p901
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2017.7377