Figure 3.

Molecules and associated signaling pathways that may mediate drug tolerance in EGFR-mutated lung cancer cells upon treatment with an EGFR TKI. Molecules known to cause drug tolerance are indicated with underlined bold letters. Molecules such as PI3K, AKT, mTOR, or c-Src may play important roles in drug tolerance [36,52], and other candidates not illustrated here include inhibited apoptosis, altered chromatin state, stabilized EGFR through a de-ubiquitinase, involvement of the tricarboxylic acid (TCA) cycle, induced ER stress, and upregulation of cholesterol synthesis.