Resistance to dual blockade of the kinases PI3K and mTOR in KRAS-mutant colorectal cancer models results in combined sensitivity to inhibition of the receptor tyrosine kinase EGFR.
Using an in vivo model for real-time siRNA delivery tracking, we show that siRNA-mediated inhibition of KRAS as well as RAF or PI3K combinations can impair KRAS-mutant colorectal cancer in xenograft models.
Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer.
Importantly, a PI3K SL gene signature containing the top hits of the SL genes identified in our meta-analysis robustly predicted overall patient survival in colorectal cancer, especially among patients with tumors with an activated PI3K pathway.
Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed.
Our findings provide evidence that EDA could play a role in tumor-induced lymphangiogenesis via upregulating autocrine secretion of VEGF-C in colorectal cancer, which is associated with the PI3K/Akt-dependent pathway.
Although TANKYRASE (TNKS) inhibitors have been proposed as promising candidates, there are many colorectal cancer models that do not respond positively to TNKS inhibition <i>in vitro</i> and <i>in vivo</i> Therefore, a combinatorial therapeutic approach combining a TNKS inhibitor (G007-LK) with PI3K (BKM120) and EGFR (erlotinib) inhibitors in colorectal cancer was investigated.
We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage.
Antitumor Efficacy of the Dual PI3K/mTOR Inhibitor PF-04691502 in a Human Xenograft Tumor Model Derived from Colorectal Cancer Stem Cells Harboring a PIK3CA Mutation.
Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer.
In short, COX-2 or 5-LOX deletion and its inhibitors enhanced activity of PTEN and suppressed cell and adenoma progression through PI3K/AKT pathway in colorectal cancer.
Taken together, down regulation of CSN5 may inhibit invasion and arrests cell cycle progression in colorectal cancer via PI3K/AKT/NF-κB signal pathway, which indicates that there is a potential of targeting CSN5 as a novel gene therapy approach for the treatment of colorectal cancer.
The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment.