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Lung cancer is the most common malignant tumor in the world with the highest incidence of deaths. In recent years, the treatment of lung cancer has made a significant breakthrough. However, as the tumor progresses, lung cancer cells inevitably acquire resistance and the efficacy of the treatment are greatly reduced. P21 protein plays a dual role in tumors, which not only regulates the cell cycle, induces apoptosis, inhibits cell proliferation, but also protects cells against apoptosis and
promotes tumor cell resistance. This article reviews the research on P21 and lung cancer resistance, to provide new ideas for individualized treatment of lung cancer and overcoming lung cancer resistance.