The vast majority of pancreatic ductal adenocarcinomas (PDAC) involve activating mutations in KRAS (KRAS*) and as with other KRAS* cancers, PDAC show minimal response to existing therapies used in the clinic. While no satisfactory KRAS*-specific drugs are currently available, inhibitors of MEK and PI3K (MEKi and PI3Ki) pathways necessary for KRAS*-mediated cellular transformation in vitro are now being introduced into clinical trials. Read more.
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Loss of function mutations in STK11, encoding the Ser/Thr protein kinase, LKB1 are responsible for the familial hamartoma syndrome, Peutz Jeghers Syndrome (PJS). Importantly, recent studies have revealed sporatic mutations in STK11 in a variety of human cancers, including lung adenocarcinomas. LKB1 phosphorylates and activates AMP dependent protein kinase in response to energy stress, and thus plays a key role in energy homeostasis. Read more.
Impairments in the ability of insulin to stimulate PI3K in liver and muscle results in insulin resistance and type 2 diabetes, while genetic aberrations that result in hyper-activation of PI3K in epithelial tissues results in cancers. Activating mutations in PIK3CA, the gene encoding the p110 [unreadable] catalytic subunit of PI3K, are among the most frequent oncogenic occurrences in epithelial cancers. Read more.
The protein NRF2 is a transcription factor, which means that its role is to regulate expression of specific genes within a cell. Among other functions, NRF2 has been shown to be involved in metabolic pathways in the cell, in which nutrients are broken down to provide energy for cellular functions Read more.