Further analysis of the acquired mutations and RNA expression in the acquired-resistant tumour for patient #4612 revealed both an acquired IRS1 P313S variant (Fig. 2b), as well as a ~5-fold decrease in the expression of the PI3K regulatory subunit PIK3R1, leading us to hypothesize that the PI3K/mTOR pathways might be dysregulated in the resistant tumour. Here, IRS1 is linked to neoplasm.