Genetic determinism of the models is also of substantial import: the presence of PIK3CA mutations and PTEN loss in certain RA-FLS lines (MH7A, SW982) engenders resistance to “pure” PI3K blockade, whereas the addition of mTOR inhibitors or the adoption of dual strategies can restore the desired phenotypic response, as corroborated by recent clinical and preclinical reviews [71,78,84]. The gene discussed is PTEN; the disease is rheumatoid arthritis.