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.
TBCRC 032 IB/II Multicenter Study: Molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR+ metastatic triple-negative breast cancer.
Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with 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.
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.
This study provides a preclinical rationale to investigate the therapeutic potential for the combination of PI3K inhibition and eribulin in the difficult to treat TNBC.
<b>Conclusion:</b> We demonstrated that DFO could upregulate expression of TfR1 and DMT1 , which enhanced iron uptake via activating IL-6/PI3K/AKT signaling pathway in aggressive TNBCs.
We review the evidence for PI3K pathway activation in TNBC, and clinical trial data for PI3K, AKT and mammalian target of rapamycin inhibitors in TNBC.
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.
Further study of underlying mechanisms demonstrated that DANCR bound with RXRA and increased its serine 49/78 phosphorylation via GSK3β, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis.
Here, we provide new evidence of the effects of exercise on TNBC prevention, control, and outcomes, based on the inhibition of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB also known as Akt)/mammalian target of rapamycin (mTOR) (PI3K-Akt-mTOR) signaling.
Mechanistically, DCC-2036 targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt-NFκB signaling to exert its antitumor effect in TNBC.
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.
Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway.
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.
CF33 was effective <i>in vitro</i> with potent cytotoxicity and efficient intracellular replication observed in TNBC lines with phosphatidylinositol 3-kinase (PI3K)/Akt pathway mutations that resulted in endogenous phospho-Akt (p-Akt) activity (BT549, Hs578T, and MDA-MB-468).