PIK3CA and cancer: To evaluate the missing PK properties of metformin in the context of cancer therapy while concurrently excluding a role for insulin in its anti-tumor action in murine cancer models, we used breast xenotumors formed by PIK3CA H1047R-mutated MCF10DCIS.com cells (Cufí et al., 2013), which proliferate in vitro irrespective of the presence or absence of insulin, and form tumors that are refractory to dietary restriction (DR) in vivo [17, 18].