Figure 4.

Summary of mechanisms of lung cancer plasticity, heterogeneity and the correlated therapeutics. This model illustrates the guidance of lung cancer plasticity and heterogeneity in clinical use, especially in drug resistance upon target therapies. Different therapeutic strategies depend on the unique mechanisms. Histologically, transition from ADC to SCC and switch from NSCLC to SCLC have been found broadly. Complete transition leads to the using of transited tumor therapy while combinational treatment is applied to partial transformation. EMT is a special aspect of phenotype alteration. It shows morphological plasticity of lung cancer with the switch of biological markers. Interfering EMT process can be a bright way to inhibit certain kind of drug resistance. In addition to histological transition, genetic adaption provides an evident proof for lung cancer heterogeneity. As the intensive study of cell and molecular mechanism, gene alteration and abnormal activation have been revealed in the drug-surviving cancer cells. More target-pointed drugs are needed, substitutionally or combinationally. Intratumor heterogeneity reinforces the composition of lung cancer that changes for adapting to the environment. A typical illustration is the acquirement of stem cell-like property, against which ATRA is an effective therapy. In terms of targeting genetic heterogeneity, identification of advantageous clones and application of combinational therapy could provide a better outcome for lung cancer patients