As opposed to other tumor types such as gliomas which were cytostatic [22], this class of inhibitor caused strong apoptosis selectively in ER+ vs TNBC models and further among those carrying mutations in PIK3CA or PTEN. Apoptosis in these models was triggered by a selective inhibition of the mTORC1 substrate 4E-BP1 and suppression of the anti-apoptotic factor MCL1, as genetic rescue of EIF4E or MCL1 both suppressed apoptosis induced by RMC-6272. Here, PIK3CA is linked to central nervous system cancer.