Generation of paired chemonaive and chemoresistant small cell lung cancer (SCLC) PDX models led to the finding that EZH2 promotes chemoresistance by epigenetically silencing SLFN11, and EZH2 inhibition prevents acquisition of chemoresistance and improves chemotherapeutic efficacy in SCLC [81]. Here, EZH2 is linked to small cell lung carcinoma.