期刊
CELLS
卷 8, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/cells8040333
关键词
mTOR signalling; metabolism; head and neck cancer; mutant genes; biomarkers; targeted therapies; clinical trials
类别
资金
- Australian National Health and Medical Research (NHMRC) [APP1049870, APP1106697]
- Association for International Cancer Research (AICR) [11-0060]
- Victorian Cancer Agency [COF11_04, MCRF16017]
- French LYriCAN grant [INCa-DGOS-Inserm_12563]
The mammalian target of rapamycin (mTOR) signalling pathway is a central regulator of metabolism in all cells. It senses intracellular and extracellular signals and nutrient levels, and coordinates the metabolic requirements for cell growth, survival, and proliferation. Genetic alterations that deregulate mTOR signalling lead to metabolic reprogramming, resulting in the development of several cancers including those of the head and neck. Gain-of-function mutations in EGFR, PIK3CA, and HRAS, or loss-of-function in p53 and PTEN are often associated with mTOR hyperactivation, whereas mutations identified from The Cancer Genome Atlas (TCGA) dataset that potentially lead to aberrant mTOR signalling are found in the EIF4G1, PLD1, RAC1, and SZT2 genes. In this review, we discuss how these mutant genes could affect mTOR signalling and highlight their impact on metabolic processes, as well as suggest potential targets for therapeutic intervention, primarily in head and neck cancer.
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