However, when quiescent TISCs are subjected to a second-hit by mutation in oncogenes, such as a targeted mutation in a negative regulator of mammalian target of rapamycin (mTOR) complex or tuberous sclerosis complex 1 (TSC1) could lead to a colossal enhancement in the proliferation of TISCs along with upregulation in mitochondrial metabolic activity as evidenced by increase mitochondrial number per cell, elevated production of reactive oxygen species (ROS) and OXPHOS activity eventually leading to tumor relapse (14). Here, MTOR is linked to neoplasm.