Evaluation of: Zhou Y, Rideout WM 3rd, Zi T et al.: Chimeric mouse tumor models reveal differences in pathway activation between ERBB family- and KRAS-dependent lung adenocarcinomas. Nat. Biotechnol. 28(1), 71-78 (2010). EGFR and KRAS mutations are among the most frequent oncogenic mutations in non-small-cell lung cancer. However, these two mutations are associated with distinct clinical presentations. The underlying mechanisms for these differences are unclear. This study by Zhou et al. examines lung cancer formation induced by oncogenic mutants of ERBB, EGFR and HER2, as well as KRAS, using a novel chimeric mouse approach. They demonstrate that the PI3K/Akt pathway is preferentially activated in ERBB-induced tumors while KRAS-induced lung cancer demonstrates strong activation of the c-Jun N-terminal kinase pathway. This result suggests that, despite the involvement of KRAS and ERBB receptors in the same signaling pathway, oncogenic KRAS and ERBB mutants utilize different cellular signals to induce cancer formation.
