A detailed molecular genetic analysis of the primary and metastatic tumors demonstrated somatic mutations in 2 well-known cancer genes associated with regulation of PI3K/AKT signaling pathway: (1) PIK3CA, which encodes the catalytic alpha subunit of the phosphoinositide-3-kinase, and (2) PTEN, which encodes phosphatase and tensin homolog.
Accumulating genetic and cancer biological studies demonstrate the importance of understanding the PI3K/Akt/mTOR and CDK4/6/RB pathways in ER+ HER2- breast cancer.
This study demonstrates that flotillins may not be suitable as cancer therapy targets in cells that carry certain other oncogenic mutations such as PI3K activating mutations, as unexpected effects are prone to emerge upon flotillin knockdown which may even facilitate cancer cell growth and proliferation.
Cancer-specific mutations in the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) p110 alpha occur in diverse tumors in frequencies that can exceed 30%.
Mutations in BAF complex and PI3K pathway genes co-occurred more frequently in TERTp-wt GBMs (p = 0.0002), an association that has been observed in other cancers, suggesting a functional interaction indicative of a distinct pathway of gliomagenesis.
Phosphatidylinositol-3-kinase (PI3K)/AKT pathway mutations are associated with cancer and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene mutations have been observed in 25-45% of breast cancer samples.
Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer.
Several pathways such as TGF-β/SMAD signaling and PI3K (phosphoinositide 3-kinase) signaling were defined as synergistic (affected by different alterations in all four cancer types).
While genetic alteration in the p85α-p110α (PI3K) complex represents one of the most frequent driver mutations in cancer, the wild-type complex is also required for driving cancer progression through mutations in related pathways.
Up to 86% of GC and 90% of CRC have at least one aberration in the PI3K pathway, and there are significant differences in the frequencies of these aberrations according to cancer type and ethnicity.
This is the first study to evaluate the role of germ line genetic variations in PI3K-AKT-mTOR pathway as cancer susceptibility factors that will help us identify high-risk individuals for bladder cancer.
These studies extend our understanding of the architecture of PI3Ks and provide insight into how two classes of mutations that cause a gain in function can lead to cancer.
Genetic phenomena that lead to constitutive pathway activation are common in human cancer; the most relevant are mutations affecting the catalytic subunit of PI3K and loss of function of the PTEN tumor suppressor.
Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas.
PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway.
The class I phosphoinositide 3-kinases (PI3Ks) are key signaling enzymes composed of a heterodimer of a p110 catalytic subunit and a p85 regulatory subunit, with PI3K mutations being causative of multiple human diseases including cancer, primary immunodeficiencies, and developmental disorders.
Recently, many reports have revealed that the PIK3CA gene which encodes the p110 catalytic subunit of PI3K kinase is mutated in many human malignancies.