As the malignant phenotype of LKB1-inactivated lung cancers are specifically dependent on aberrant CRTC co-activation of the oncogenic CREB transcriptional program, targeting the CRTC-CREB interaction, hence, the active CRTC-CREB transcription complex, may selectively inhibit LKB1-deficient tumors with minimal effects on normal cells as demonstrated by our data. Here, CALR is linked to lung cancer.