7143575930Figure 1: mTOR activity is usually increased in most cancers. This is usually because of mutations in or amplification of Akt, PI3, PTEN, or other growth factors upstream of mTOR. In some cases however mutations within mTOR actually cause greater mTOR expression.
Cancer is the uncontrolled growth of abnormal cells. Many key changes occur to transform a normal cell into a cancerous one. In most cancers this is the result of dysregulation of core regulatory proteins and complexes. Most cancerous cells will dysregulate the mTOR complexes leading to uncontrolled cell growth (Figure 1). Mammalian target of rapamycin (mTOR) is a kinase that regulates cell growth and proliferation. When unregulated, an increased expression of mTOR leads to increased cell growth. Tuberous sclerosis complex is an autosomal dominant disease in which mutations in TCS1 and TCS2 results in unregulated constitutive activation of the mTOR complex 1 [1]. This causes benign tumors to grow in almost every organ. mTOR mutations have been found in the following cancers (Figure 2). The S2215Y mutation has also been found to increase the S phase of the cell cycle. This is important for cell proliferation as this is the phase that DNA is replicated [2].
Figure 2: The cancers above are linked with specific single amino-acid changes on the mTOR protein.
mTOR inhibitors such as rapamycin may be effective at treating these cancers. There have only been a few mTOR inhibitors approved for treatment and only in advanced cancers, while clinical trials have shown that inhibitors improve survival of the patient they do not entirely remove the cancer [3]. This could be a bias though however because the treatments are only for advanced cancers. The major side effect of mTOR inhibitors is the reduction of the immune system, which is why these inhibitors are used in preventing rejection of organ transplants. This could be a double edged sword in the treatment of cancers with mTOR inhibitors. mTOR inhibitors and knowing more of how mTOR induces helps transform a normal cell into a cancerous cell is still a hot topic for drug targeting in cancer research.