TSC1 and neoplasm: Nevertheless, inhibition of the mTOR pathway has been observed with metformin without its effects on LKB1, AMPK, and TSC1/2 signaling, indicating its off-target mechanisms regulating the activation of the phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mTOR signaling pathways in tumor cells [53, 54].