Clonal variants or subpopulations have been isolated from every major histological type of cancer, and cellular heterogeneity in lung cancer is a common occurrence. These subpopulations may exhibit differences in drug resistance and invasive potential. One therefore needs to consider the subpopulations as well as the tumour to overcome the barriers of drug resistance and metastasis for successful treatment. Isogenic variants of cancer cell lines can be very valuable in providing controlled human experimental systems to study clinically relevant parameters such as drug resistance and invasiveness. These variants can be established by selection based on a characteristic of the subpopulation or by isolating clonal subpopulations from a heterogeneous population. Drug-resistant variants can be generated by pulse selection, which usually generates low-level resistance, which may as well be clinically relevant, or by continuous exposure, which can be used to obtain high-level resistant variants. Clonal subpopulations may also be isolated based on morphological differences using simple cell-culture-based techniques.
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