Based on our previous findings, including 1) NNK-induced exocytosis of IGF2 via VDCC-intervened Ca2+ influx [25, 42]; 2) the efficacy of antagonizing Ca2+ signaling in preventing NB-induced lung tumor formation in vivo [19], and 3) reduced lung cancer diagnosis via clinically available CCB medication, we hypothesized that chronic NB exposure induces excessive IGF2 signaling in AT2s through at least two independent but comparable mechanisms. The gene discussed is IGF2; the disease is lung cancer.