TSC1 and breast cancer: Buparlisib, originally developed for HER2- breast cancer but abandoned due to high toxicity and suboptimal results, is a pan-isoform class I PI3K inhibitor evaluated in a Phase II study (NCT01551030) of 13 patients but it did not meet its primary endpoints even in TSC1-altered patients and was associated with significant toxicity and currently has no FDA approvals [61].