In this review we outline the role of PI3K in the development and progression of CRC and discuss data from current and ongoing clinical trials targeting this pathway.
Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3β/β-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC.
Therefore, the purpose of this study was 2-fold: 1) to analyze the distribution pattern of PI3K pathway components in human normal colorectal cancers, and 2) to determine whether targeted inhibition of PI3K inhibits colon cancer growth in vitro and suppresses metastatic growth in vivo.
Although AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional antitumor activity.
Based on the above‑mentioned results, the dual PI3K/mTOR and ATP‑competitive mTOR inhibitors have demonstrated high potential for targeting the mTOR pathway in CRC.
We showed that Parathyroid Hormone-related Peptide (PTHrP) induces proliferation, migration, survival and chemoresistance via MAPKs and PI3K/AKT pathways in colorectal cancer (CRC) cells.
CONCLUSIONS OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3ß-ß/catenin pathway.
Two main elements of the PI3K-Akt signaling pathway, phosphatase and tensin homolog deleted on chromosome 10 and B-cell lymphoma 2-associated agonist of cell death, were demonstrated to be downregulated in CRC.
However, HSP27 expression in CRCs was strongly associated with the co-presence of wildtype KRAS and activated PI3K/AKT (p=0.004), indicating a possible role of HSP27 in overcoming PI3K/AKT induced OIS in tumours.
Our previous study demonstrated that administration of NVP-BEZ235 (BEZ235), a dual PI3K/mTOR inhibitor, before radiotherapy (RT) enhanced the radiotherapeutic effect in colorectal cancer (CRC) cells both in vitro and in vivo.
Brahma-related gene-1 has an important role in the process of CRC development by activating the PI3K-Akt signalling pathway and resultant upregulation of cyclin D1 levels.