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There are preclinical data suggesting that the combination of EGFR-TKI and CDK4/6 inhibitors may therefore be beneficial in co-mutated EGFR and CDKN2A patients as it may prevent gain of resistance against TKIs [96]

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"Whether these effects actually contribute to increased disease risk cannot be determined from this study, but this demonstration that smoking-associated epigenetic changes have functional relevance is important

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