inhibitors and results showed increased selectivity to mtor by 26000 fold. limitations of new generation mtor inhibitors although the new generation of mtor inhibitors hold great promise for anticancer therapy and are rapidly moving into clinical trials, there are many important issues that determine their success in the clinic. first of all predictable biomarkers for benefit of these inhibitors are not available. it appears that genetic determinants predispose cancer cells to be sensitive or resistant to these compounds. tumors that depend on pi3k/mtor pathway should respond to these agents but it is unclear if compounds are effective in cancers with distinct genetic lesions. inhibition of mtor is a promising strategy for treatment of number of cancers. limited clinical activity of selective mtorc1 agents have made them unlikely to have impact in cancer treatment. the development of competitive atp-catalytic inhibitors have the ability to block both mtorc1 and mtorc2. future the limitations of currently available rapalogs have led to new approaches to mtor targeting. studies suggest that mtor inhibitors may have anticancer activity in many cancer types, such as rcc, neuroendocrine tumors, breast cancer, hepatocellular carcinoma, sarcoma, and large b-cell lymphoma. one major limitation for the development of mtor inhibition therapy is that biomarkers are not presently available to predict which patient will respond to them. a better understanding of the molecular mechanisms that are involved in the response of cancer cells to mtor inhibitors are still required so this can be possible. a way to overcome the resistance and improve efficacy of mtor targeting agents may be with stratification of patients and selection of drug combination therapies. this may lead to a more effective and personalized cancer therapy. although further research is needed, mtor targeting still remains an attractive and promising therapeutic option for the treatment of cancer.