ALK and cancer: In contrast, non-smoking-related lung cancers are notably enriched for targetable genetic alterations, with 78%-92% of these cancers harboring clinically actionable changes, such as EGFR mutations and ALK fusions.22,25 Furthermore, non-smoking-related lung cancers exhibit a significantly lower tumor mutational burden (TMB) than their smoking-related counterparts, being 7-fold lower, and show a depletion of smoking-related genetic signatures; only 6% contain such signatures, which may reflect secondhand smoke exposure.26