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The large Ser/Thr protein kinase mTOR signals through two physically distinct multipro- tein complexes called mTOR complexes 1 and 2(mTORC1 and mTORC2). The mTORC1 pathway integrates inputs from nutrients and growth factors for protein synthesis, autophagy, cell growth and proliferation. Dietary restriction delays ageing and extends life span in diverse species including yeast, worm, fly, and mammals such as mouse and monkey. Because in- cidences of many diseases such as cancer, cardiovascular disease, metabolic disease and dementia rise rapidly with age, interventions that delay ageing would greatly benefit health. It has become apparent in recent years that the nutrient sensing mTOR pathways are well con- served among such various species and important regulators of ageing and longevity.

Molecular alteration of PI3K and mTOR pathways is frequently detected in various types of cancers. PIK3CA mutations are the predictive markers for anti-EGFR antibodies, trastuzumab, and lapatinib. The p110 isoform selective PI3K inhibitors has been developed in the clinical settings to reduced off-target induced adverse events. Feedback loop for PI3K signal leads the resistance to PI3K inhibitors. Dual PI3K/mTOR inhibitors and mutation selective PI3K inhibitors are under evaluation to circumvent the resistance.

Basic, clinical and translational metabolic researches in cancer area have been extensively tried to discover and develop novel cancer metabolism drugs. Since tumor cells have metabolic dependencies that distinguish them from their normal counterparts, targeted inhibition of these metabolic dependencies is considered a promising therapeutic strategy against cancer. For example the representative cancer metabolism is that cancer cells exhibit profound metabolic alterations by choosing aerobic glycolysis to metabolize glucose to lactate regardless of the presence of adequate oxygen, although normal cells which mainly utilize glucose by using mitochondrial oxidative phosphorylation to generate ATP. In this review, we focus on several important oncogenes and enzymes, whose alterations have contributed extensively to the metabolic phenotype of cancer cells, with an emphasis on the therapeutic targets.