Especially after VDA treatment, a remaining viable tumor rim, characterized by intratumor overexpression of hypoxia-inducible factor 1α (HIF-1α) and enhanced oxidative stress mediated by tumor-associated macrophages (TAMs), is responsible for selecting aggressive tumor cell phenotypes ready to escape oxygen and nutrient deprivation and thus, accelerating the undesired outcome of the disease4–6. The gene discussed is HIF1A; the disease is neoplasm.