Integrin β1, myosin light chain kinase and myosin IIA are required for activation of PI3K-AKT signaling following MEK inhibition in metastatic triple negative breast cancer.
Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613.
Mechanistically, DCC-2036 targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt-NFκB signaling to exert its antitumor effect in TNBC.
Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca(2+) signaling pathway in triple-negative breast cancer (TNBC) cells.
Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination.
Mutational profiles in triple-negative breast cancer defined by ultradeep multigene sequencing show high rates of PI3K pathway alterations and clinically relevant entity subgroup specific differences.
Phosphatidylinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression and protein levels, and mTOR inhibitors have been shown to inhibit growth in TNBC cell lines.
Poly(ADP‑ribose) polymerase (PARP) inhibitors, phosphatidylinositol 3‑kinase (PI3K) inhibitors and carboplatin (CBP) have demonstrated sufficient efficacy and safety for their use as individual drugs for the treatment of TNBC; however, their effects on TNBC when used as a combination have not been investigated.
TBCRC 032 IB/II Multicenter Study: Molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR+ metastatic triple-negative breast cancer.
TET1 expression correlated with sensitivity to drugs targeting the PI3K-mTOR pathway, and CRISPR-mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes, and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression.
The addition of PI3K-mTOR inhibitors to cisplatin or paclitaxel increased the activity of chemotherapy in the TNBC and LGSOC models; whereas no added activity was observed in the LADC model.
The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and drug sensitivity has been associated with activation of PI3K or AKT and/or deletions of PTEN.
The development of drugs targeting the PI3K/AKT/mTOR pathway for the treatment of TNBC is an evolving field that should take into account the efficacies and toxicities of new agents in addition to their interactions with different cancer pathways.
The main aim of this study was to evaluate whether overexpressing inositol polyphosphate 4-phosphatase type II (INPP4B) gene, a novel tumor suppressor gene negatively regulating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, could enhance the antitumor efficacy of PARP inhibitor AG014699 used in the treatment of triple-negative breast cancer (TNBC).
The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways.
The overall findings suggest that Chetomin inhibited the growth of human TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling and could be used as a novel chemotherapeutic agent for the treatment of human TNBC in future.
The present study examined the effects of tetrandrine suppressing proliferation, targeting LC3, p62, and Beclin-1 autophagy genes by inhibiting PI3K/AKT/mTOR signaling in Triple-negative breast cancer (TNBC) MDA-MB-231 cell.
This review discusses the potentials and drug discovery perspectives of PI3K/AKT/mTOR as a therapeutic target for effective management of TNBC with anticipated challenges.
This review will focus on recent therapeutic innovations for TNBC, including poly-ADP-ribosyl polymerase (PARP) inhibitors, phosphoinositide 3-kinase (PI3K) pathway inhibitors, immune checkpoint inhibitors, and cyclin-dependent kinase (CDK) inhibitors.