Our study demonstrates a genetic selectivity of MK2206 in inhibiting thyroid cancer cells by targeting the PI3K/Akt pathway, supporting a clinical trial in thyroid cancer.
Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-beta-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities.
The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathway, such as <i>RAS</i> and <i>BRAF</i>, or by the rearrangement of growth factor receptor tyrosine kinase genes such as <i>RET/PTC</i>.
These distinct genetic alterations constitutively activate the MAPK, PI3K and β-catenin signaling pathways, which have been implicated in thyroid cancer development and progression.
This genotype-based targeting of the PI3K/Akt pathway using Akt and mTOR inhibitors may offer an effective therapeutic strategy for thyroid cancer and warrants further studies.
This provides an explanation for the reciprocal relationship of rs17849071G/T with FTC, since PIK3CA amplification is an important oncogenic mechanism in thyroid cancer, particularly FTC.
We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3'-OH kinase (PI3K)/Akt pathways.