P2, N=110, Recruiting, Dana-Farber Cancer Institute | N=180 --> 110

By applying the pathway inhibitor LY294002, it was confirmed that the PI3K/Akt pathway is crucial for osteosarcoma proliferation. This study confirms that PYCR1 drives osteosarcoma cell proliferation and migration through three key mechanisms: regulating downstream genes, inhibiting ferroptosis, and activating the PI3K/Akt signaling pathway.

In vivo, capivasertib significantly suppressed tumor growth and its combination with cisplatin significantly prolonged survival in xenograft models without inducing overt systemic toxicity. Mechanistically, capivasertib treatment increased AKT phosphorylation, consistent with pharmacodynamic target engagement, while suppressing downstream mTOR/4EBP1 signaling and inducing pro-apoptotic levels. Collectively, these findings demonstrate that Akt/mTOR inhibition by capivasertib enhances therapeutic efficacy in preclinical NPC models and provides rationale for further clinical evaluation of capivasertib in advanced NPC.

Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a "PI3K/AKT-STAT5A-TRIM21-PARP1" axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy.

Functional relevance of AKT signaling was evaluated using siRNA knockdown, MK2206, and SC79...EEDJF exerts anti-colorectal cancer effects in vitro, potentially associated with regulation of PI3K-Akt/p21 signaling. These findings provide a basis for further studies on the bioactive constituents, pharmacological mechanisms, and in vivo efficacy of DJF-derived preparations.

GOLPH3, which is overexpressed in PRAD, may enhance glucose metabolic activity in PRAD cells in association with activation of the PI3K/AKT/mTOR pathway, thereby supporting PRAD cell proliferation. These findings provide basic mechanistic evidence for the role of GOLPH3 in PRAD cell metabolism, but further clinical studies are required to determine its prognostic or therapeutic relevance.

Furthermore, the PI3K/AKT inhibitor LY294002 enhanced the effects of sh-MUC1 on the proliferation, apoptosis, migration, invasion and EMT progress, while the activator SC79 partially restored these effects...To conclude, these findings suggested that MUC1 played an important role in lung cancer progression, potentially through the PI3K/AKT pathway. This positioned MUC1 as a molecule worthy of further investigation for its therapeutic potential.

These net costs amount to $0.88 per-member-per-month. While introduction of capivasertib could reduce adverse event and follow-up costs, it may result in an overall increase in payers' budget.

Notably, low-dose Capivasertib, an AKT inhibitor targeting tumors with PIK3CA/AKT1/PTEN mutation(s), induced senescence selectively in FUCA2-high LUAD irrespective of PIK3CA/AKT1/PTEN/TP53 mutational status, and its combination with the nutraceutical senolytic procyanidin C1 achieved potent and low-toxicity suppression of LUAD across multiple preclinical models. Together, our results uncover the FUCA2-ErbB3 fucosylation-AKT pathway as a central regulator of senescence and propose a FUCA2-guided drug repurposing strategy for LUAD.

EIF3B activated PI3K/AKT signaling and EMT, both of which were abolished by miR-124-3p or LY294002. These findings define the miR-124-3p/EIF3B/PI3K-AKT axis as a key regulator of OSCC progression and suggest EIF3B as a potential prognostic biomarker and therapeutic target.

PI3K/AKT/mTOR pathway activity was examined by Western blot, and its function validated using SC79 (AKT activator) and LY294002 (PI3K inhibitor)...By modulating the PI3K/AKT/mTOR signaling axis and the pro-angiogenic microenvironment, ADGRD1 facilitates tumor growth and neovascularization. ADGRD1 may serve as a promising prognostic biomarker and therapeutic target for advanced BLCA.