The mammalian target of rapamycin (mTOR) kinase is a key regulator of protein synthesis that links nutrient sensing to cell growth and cancer. This study reveals that oncogenic mTOR signaling specifically regulates a set of genes involved in cell proliferation, metabolism, and invasion. Using ribosome profiling, the researchers identified 144 mTOR-sensitive target genes, many of which are involved in cancer progression. They also developed a clinically relevant mTOR inhibitor, INK128, which reprograms gene expression to reduce prostate cancer metastasis. The study shows that mTOR signaling regulates the translation of specific mRNAs, which are crucial for cancer cell invasion and metastasis. These findings highlight the importance of mTOR signaling in cancer progression and suggest that targeting mTOR could be a promising therapeutic strategy for prostate cancer. The study also identifies a novel regulatory element, the pyrimidine-rich translational element (PRTE), which is involved in mTOR-sensitive gene regulation. The results demonstrate that mTOR signaling can be targeted with ATP site inhibitors, such as INK128, to inhibit cancer progression. The study provides a comprehensive understanding of how mTOR signaling influences cancer cell behavior and offers new insights into the therapeutic potential of mTOR inhibitors in cancer treatment.The mammalian target of rapamycin (mTOR) kinase is a key regulator of protein synthesis that links nutrient sensing to cell growth and cancer. This study reveals that oncogenic mTOR signaling specifically regulates a set of genes involved in cell proliferation, metabolism, and invasion. Using ribosome profiling, the researchers identified 144 mTOR-sensitive target genes, many of which are involved in cancer progression. They also developed a clinically relevant mTOR inhibitor, INK128, which reprograms gene expression to reduce prostate cancer metastasis. The study shows that mTOR signaling regulates the translation of specific mRNAs, which are crucial for cancer cell invasion and metastasis. These findings highlight the importance of mTOR signaling in cancer progression and suggest that targeting mTOR could be a promising therapeutic strategy for prostate cancer. The study also identifies a novel regulatory element, the pyrimidine-rich translational element (PRTE), which is involved in mTOR-sensitive gene regulation. The results demonstrate that mTOR signaling can be targeted with ATP site inhibitors, such as INK128, to inhibit cancer progression. The study provides a comprehensive understanding of how mTOR signaling influences cancer cell behavior and offers new insights into the therapeutic potential of mTOR inhibitors in cancer treatment.