Genetically engineered mouse (GEM) models of BRAF -mutated melanoma display differential responses to inhibition of the mitogen activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K) pathway.

The present study aimed to explore the biological characteristics of non-small cell lung cancer (NSCLC) cells and the mechanism of chemosensitivity through the role of the PI3K/Akt/mTOR signaling pathway mediated by BRAF gene silencing.

Sep 20, 2018 · We now show, that PI3K/AKT signalling via potent oncogenic PIK3CA and AKT3 mutants, is not sufficient to overcome proliferative arrest induced by BRAF/MEK inhibition, but rather enables the...

We demonstrate that activation of the PI3K/AKT pathway is a mechanism of both innate and acquired resistance to BRAF inhibitors in BRAFV600E CRC, and suggest combinatorial approaches to improve outcomes in this poor prognosis subset of patients.

In our study, we investigated the MEK inhibitor selumetinib and PI3K/mTOR dual inhibitor BEZ235 alone and in combination in BRAF-only mutant and BRAF + PI3K/PTEN double mutant cancer cells using short- and long-term 2D viability assays, spheroid assays, and immunoblots.

Jun 3, 2021 · Activation of the PI3K/Akt/mTOR signaling pathway may reverse the role of silencing of BRAF gene expression, providing a potential approach for improving the chemosensitivity of NSCLC.

Jun 16, 2015 · BRAF and MEK inhibitors have improved outcomes for patients with BRAF -mutant melanoma, but their efficacy is limited by both intrinsic and acquired resistances. Activation of the PI3K pathway can mediate resistance to these agents, providing a strong rationale for combination therapy in melanoma.

Nov 20, 2023 · The combination of MAPK and PI3K inhibitors reversed BrafV637E oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro.

Jan 23, 2024 · Aberrant PI3K/AKT signaling in BRAF -mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF -mutated solid tumors (ClinicalTrials.gov identifier NCT01902173).

Apr 8, 2012 · In addition to increased activation of BRAF and MEK, members of the phosphoinositide 3-kinases (PI3K) pathway are elevated in metastatic melanoma (17), and inhibition of PI3K/mTOR reduces the growth of tumors in melanoma model systems (18).