The Lamarckian model of acquired resistance could be mechanistically related to the arising in melanoma of two predominant cell populations, with distinct phenotypic states, termed as “invasive” (AXL high/MITF low) and “proliferative” (AXL low/MITF high) phenotypes, which harbor “signature” gene expression profiles, induced upon activation of distinct transcriptional programs [19,20]. The gene discussed is AXL; the disease is melanoma.