Figure 2.
Potential targeting of PI3K/mTORC1 signaling in hamartoma syndromes. Germline mutations of PTEN, LKB1, TSC1 and TSC2 genes lead to upregulation of PI3K/mTORC1 signaling and are associated with spectrum of hamartoma syndromes (Light blue boxes). Blue coloring indicate tumor suppressor proteins, negatively regulating mTORC1 signaling. Germline mutations of PTEN is associated with Cowden syndrome (CS), Lhermitte-Duclos disease (LDD), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-Like syndrome; germline mutations of LKB1 is associated with Peutz-Jeghers syndrome (PJS), TSC1 or TSC2 mutations is associated with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM). Pink coloring indicate inhibitors of PI3K/ mTORC1 signaling pathway, which may have promising therapeutic effects for treatment of hamartoma syndromes. Rapamycin and it analogs CCI-779, RAD001 and AP23573 are to inhibit mTORC1; PI-103, SF11206 and ZSTK474 are pan-PI3K inhibitors; NVP-BEZ235 and XL765 simultaniously target mTORC1 and PI3K.