It is possible that direct targeting of embryonic pathways might be more effective against both stem and dedifferentiating tumor cells (Takebe et al., 2011; Medema, 2013; Pattabiraman and Weinberg, 2014), and cancers “addicted to” upregulated embryonic pathway activity (e.g., Wnt in CRC and PIK3CA in metastatic breast cancer), combined with high tumor heterogeneity, might be more vulnerable to such therapies (Bienz and Clevers, 2000; Segditsas and Tomlinson, 2006; Hernandez-Aya and Gonzalez-Angulo, 2011). The gene discussed is PIK3CA; the disease is colorectal carcinoma.