In addition, AKR1C3 overexpression promoted aerobic glycolysis in HSCs by activating the AKT/mTOR pathway, but these effects were partly reversed by glycolysis inhibitors (2-DG) and AKT inhibitors (MK-2206). Our findings revealed the mechanism by which AKR1C3 promotes LF, suggesting that AKR1C3 may serve as a potential therapeutic target for LF, warranting further studies.

In the CAPItello-291 trial, capivasertib and fulvestrant demonstrated efficacy in patients with up to two prior lines endocrine therapy, but its use in late-line settings has not yet been reported. In this article, we report a case of a woman with metastatic recurrent breast cancer who was treated with capivasertib and fulvestrant was used as the late-line treatment, resulting in a progression-free survival of 8 months.

P2, N=47, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2025 --> May 2026

P1, N=20, Not yet recruiting, AstraZeneca

P3, N=300, Recruiting, AstraZeneca | N=560 --> 300

This study underscores the dual role of CSF1 in regulating both tumor survival and M2 macrophage activation in HNSCC. Targeting the DKK1/CSF1 axis may represent a promising strategy to overcome chemoresistance by disrupting tumor-macrophage crosstalk and reprogramming the immunosuppressive microenvironment.

P3, N=101, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

These findings revealed a previously undefined mechanism of action of GSK690693 as a Hippo pathway inhibitor, underscoring its efficacy in mitigating ER-positive breast cancer progression. Given the broader implications of Hippo pathway dysregulation in multiple cancers, GSK690693 could be part of a combination regimen for various malignancies.

P1, N=36, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2026 --> May 2027

Top-ranked peptides, such as Gitoxoside (- 11.53 kcal/mol) and 9-Fluoro-11 (- 11.38 kcal/mol), demonstrated stronger binding to AKT1 than the reference inhibitor Capivasertib (- 8.50 kcal/mol)...Collectively, this integrative AI framework efficiently explores peptide chemical space, enabling the rapid identification of peptide-based and peptidomimetic inhibitors with strong binding affinity and stability. The findings highlight the potential of AI-assisted peptide design as a scalable and cost-effective strategy for developing next-generation therapeutics against endometrial cancer.

Additionally, wt-EGFR and pAKTSer473 protein complex formation in A549 cells was disrupted with an AKT inhibitor (MK2206), resulting in enhanced cytotoxicity in vitro. Our study demonstrates that EGFR-TKI response in wt-EGFR cells is dictated by BRG1 status. These findings propose screening of wt-EGFR NSCLC patients for BRG1 status for identifying individuals likely to benefit from EGFR-TKI therapy versus patients who will benefit from AKT inhibitor treatment.

Considering the metabolism of icariin into icaritin in vivo, icaritin was selected for in vitro study. Furthermore, MK2206 upregulated the expression levels of cleaved caspase-3 and p-p53(Ser15), as well as the Bax/Bcl-2 ratio, and downregulated the expression levels of p-Akt(Ser473) and p-MDM2(Ser166). These findings suggest that icariin protects against high-fat diet-induced spermatogonium apoptosis potentially through regulation of Akt/MDM2/p53 signaling and promotion of mitochondrial fusion.